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Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 March 2016) | Viewed by 179586

Special Issue Editors

Prof. Dr. Aiping Lu

E-Mail Website
Guest Editor
Institute of Integrated Bioinfomedicine & Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
Interests: targeted delivery; aptamer; computer-aided drug design; natural product; small molecule drugs
Special Issues, Collections and Topics in MDPI journals
Assoc. Prof. Dr. Ge Zhang

E-Mail Website
Guest Editor
Institute for Advancing Translational Medicine in Bone & Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
Interests: targeted delivery; aptamer; computer-aided drug design; natural product; small molecule drugs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It has been known that updated understandings in the pathogenic and pathophysiological mechanisms of challenging diseases provides a very detailed picture, in which specific dysregulated molecules within certain cells could be featured. Thus, specific dysregulated molecules should be targeted as “drug targets”. More importantly, the modulation of the drug targets should be strictly localized in those specific cells (target cells) to reduce exposure to non-target cells with respect to unexpected safety concerns. Molecule-targeted and cell-targeted strategic elements should definitely be taken into consideration in drug design. Currently, molecule-targeted strategies can be achieved by computer-aided drug design. In addition, natural products, featured as multi-structures in the natural world, provide a great screening resource for molecule-targeted strategies prior to identification. On the other hand, cell-targeted strategies can be achieved by targeted-delivery systems. In the past few years, state-of-the-art technology has made rapid progress in the above-mentioned research fields.

This Special Issue, “Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product”, will cover a selection of recent research topics and current review articles in the field. Experimental papers, up-to-date review articles, and commentaries are all welcome.

Associate Prof. Dr. Ge Zhang
Prof. Dr. Aiping Lu
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


Keywords

  • targeted delivery
  • computer-aided drug design
  • aptamer
  • cell-specific delivery
  • small molecule drug
  • natural product
  • herbal medicine
  • drug screening

Published Papers (24 papers)

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Research

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4909 KiB  
Article
Synthesis, Bioevaluation and Molecular Dynamic Simulation Studies of Dexibuprofen–Antioxidant Mutual Prodrugs
by Zaman Ashraf, Alamgeer, Raqiqatur Rasool, Mubashir Hassan, Haseeb Ahsan, Samina Afzal, Khurram Afzal, Hongsik Cho and Song Ja Kim
Int. J. Mol. Sci. 2016, 17(12), 2151; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17122151 - 21 Dec 2016
Cited by 10 | Viewed by 6510
Abstract
Dexibuprofen–antioxidant conjugates were synthesized with the aim to reduce its gastrointestinal effects. The esters analogs of dexibuprofen 5a–c were obtained by reacting its –COOH group with chloroacetyl derivatives 3a–c. The in vitro hydrolysis data confirmed that synthesized prodrugs [...] Read more.
Dexibuprofen–antioxidant conjugates were synthesized with the aim to reduce its gastrointestinal effects. The esters analogs of dexibuprofen 5a–c were obtained by reacting its –COOH group with chloroacetyl derivatives 3a–c. The in vitro hydrolysis data confirmed that synthesized prodrugs 5a–c were stable in stomach while undergo significant hydrolysis in 80% human plasma and thus release free dexibuprofen. The minimum reversion was observed at pH 1.2 suggesting that prodrugs are less irritating to stomach than dexibuprofen. The anti-inflammatory activity of 5c (p < 0.001) is more significant than the parent dexibuprofen. The prodrug 5c produced maximum inhibition (42.06%) of paw-edema against egg-albumin induced inflammation in mice. Anti-pyretic effects in mice indicated that prodrugs 5a and 5b showed significant inhibition of pyrexia (p < 0.001). The analgesic activity of 5a is more pronounced compared to other synthesized prodrugs. The mean percent inhibition indicated that the prodrug 5a was more active in decreasing the number of writhes induced by acetic acid than standard dexibuprofen. The ulcerogenic activity results assured that synthesized prodrugs produce less gastrointestinal adverse effects than dexibuprofen. The ex vivo antiplatelet aggregation activity results also confirmed that synthesized prodrugs are less irritant to gastrointestinal mucosa than the parent dexibuprofen. Molecular docking analysis showed that the prodrugs 5a–c interacts with the residues present in active binding sites of target protein. The stability of drug–target complexes is verified by molecular dynamic simulation study. It exhibited that synthesized prodrugs formed stable complexes with the COX-2 protein thus support our wet lab results. It is therefore concluded that the synthesized prodrugs have promising pharmacological activities with reduced gastrointestinal adverse effects than the parent drug. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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1829 KiB  
Article
Synthesis, Biological Activity, and Apoptotic Properties of NO-Donor/Enmein-Type ent-Kauranoid Hybrids
by Dahong Li, Xu Hu, Tong Han, Shengtao Xu, Tingting Zhou, Zhenzhong Wang, Keguang Cheng, Zhanlin Li, Huiming Hua, Wei Xiao and Jinyi Xu
Int. J. Mol. Sci. 2016, 17(6), 747; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17060747 - 24 May 2016
Cited by 15 | Viewed by 4698
Abstract
Herein, we reported on a series of synthetic nitric oxide-releasing enmein-type diterpenoid hybrids (9a–i). All the target compounds showed potent antibacterial activity against selected Gram-positive bacteria S. aureus and B. subtilis. The antiproliferative activity against human tumor K562, [...] Read more.
Herein, we reported on a series of synthetic nitric oxide-releasing enmein-type diterpenoid hybrids (9a–i). All the target compounds showed potent antibacterial activity against selected Gram-positive bacteria S. aureus and B. subtilis. The antiproliferative activity against human tumor K562, MGC-803, CaEs-17 and Bel-7402 cells, and human normal liver cells L-02 was tested and the structure activity relationships (SARs) were also concluded. Compounds 9b and 9d showed the best activity against S. aureus and B. subtilis with the same minimal inhibitory concentrations (MICs) of 4 and 2 μg/mL, respectively. The derivative 9f displayed IC50 values of 1.68, 1.11, 3.60 and 0.72 μM against the four cancer cell lines above and 18.80 μM against normal liver cells L-02; meanwhile, 9f also released a high level of NO at the time point of 60 min of 22.24 μmol/L. Furthermore, it was also found that 9f induced apoptosis via the mitochondria-related pathway and arrested cell cycle of Bel-7402 cells at S phase. These findings might be important to explore new chemical entities for the main causes of in-hospital mortality of S. aureus infection, combined with a solid tumor. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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3087 KiB  
Article
Triptolide Modulates TREM-1 Signal Pathway to Inhibit the Inflammatory Response in Rheumatoid Arthritis
by Danping Fan, Xiaojuan He, Yanqin Bian, Qingqing Guo, Kang Zheng, Yukun Zhao, Cheng Lu, Baoqin Liu, Xuegong Xu, Ge Zhang and Aiping Lu
Int. J. Mol. Sci. 2016, 17(4), 498; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17040498 - 02 Apr 2016
Cited by 88 | Viewed by 8222
Abstract
Triptolide (TP), an active component isolated from Tripterygiumwilfordii Hook F, has therapeutic potential against rheumatoid arthritis (RA). However, the underlying molecular mechanism has not been fully elucidated. The aim of this study is to investigate the mechanisms of TP acting on RA [...] Read more.
Triptolide (TP), an active component isolated from Tripterygiumwilfordii Hook F, has therapeutic potential against rheumatoid arthritis (RA). However, the underlying molecular mechanism has not been fully elucidated. The aim of this study is to investigate the mechanisms of TP acting on RA by combining bioinformatics analysis with experiment validation. The human protein targets of TP and the human genes of RA were found in the PubChem database and NCBI, respectively. These two dataset were then imported into Ingenuity Pathway Analysis (IPA) software online, and then the molecular network of TP on RA could be set up and analyzed. After that, both in vitro and in vivo experiments were done to further verify the prediction. The results indicated that the main canonical signal pathways of TP protein targets networks were mainly centered on cytokine and cellular immune signaling, and triggering receptors expressed on myeloid cells (TREM)-1 signaling was searched to be the top one shared signaling pathway and involved in the cytokine and cellular immune signaling. Further in vitro experiments indicated that TP not only remarkably lowered the levels of TREM-1 and DNAX-associated protein (DAP)12, but also significantly suppressed the activation of janus activating kinase (JAK)2 and signal transducers and activators of transcription (STAT)3. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in lipopolysaccharides (LPS)-stimulated U937 cells also decreased after treatment with TP. Furthermore, TREM-1 knockdown was able to interfere with the inhibition effects of TP on these cytokines production. In vivo experiments showed that TP not only significantly inhibited the TREM-1 mRNA and DAP12 mRNA expression, and activation of JAK2 and STAT3 in ankle of rats with collagen-induced arthritis (CIA), but also remarkably decreased production of TNF-α, IL-1β and IL-6 in serum and joint. These findings demonstrated that TP could modulate the TREM1 signal pathway to inhibit the inflammatory response in RA. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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1416 KiB  
Article
Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen
by Fabio Selis, Giuseppina Focà, Annamaria Sandomenico, Carla Marra, Concetta Di Mauro, Gloria Saccani Jotti, Silvia Scaramuzza, Annalisa Politano, Riccardo Sanna, Menotti Ruvo and Giancarlo Tonon
Int. J. Mol. Sci. 2016, 17(4), 491; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17040491 - 01 Apr 2016
Cited by 27 | Viewed by 7442
Abstract
PEGylation of biomolecules is a major approach to increase blood stream half-life, stability and solubility of biotherapeutics and to reduce their immunogenicity, aggregation potential and unspecific interactions with other proteins and tissues. Antibodies have generally long half-lives due to high molecular mass and [...] Read more.
PEGylation of biomolecules is a major approach to increase blood stream half-life, stability and solubility of biotherapeutics and to reduce their immunogenicity, aggregation potential and unspecific interactions with other proteins and tissues. Antibodies have generally long half-lives due to high molecular mass and stability toward proteases, however their size lowers to some extent their potential because of a reduced ability to penetrate tissues, especially those of tumor origin. Fab or otherwise engineered smaller fragments are an alternative but are less stable and are much less well retained in circulation. We have here investigated the effects of various PEGylations on the binding properties and in vivo half-life of Fab fragments derived from the enzymatic splitting of Trastuzumab. We find that PEGylation increases the half-life of the molecules but also strongly affects the ability to recognize the target antigen in a way that is dependent on the extent and position of the chemical modification. Data thus support the concept that polyethylene glycol (PEG) conjugation on Trastuzumab Fabs increases half-life but reduces their affinity and this is a fine balance, which must be carefully considered for the design of strategies based on the use of antibody fragments. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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6528 KiB  
Article
TFE3 Alleviates Hepatic Steatosis through Autophagy-Induced Lipophagy and PGC1α-Mediated Fatty Acid β-Oxidation
by Jie Xiong, Kezhou Wang, Jiangping He, Guangya Zhang, Dandan Zhang and Fengling Chen
Int. J. Mol. Sci. 2016, 17(3), 387; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17030387 - 18 Mar 2016
Cited by 40 | Viewed by 8933
Abstract
Autophagy flux deficiency is closely related to the development of hepatic steatosis. Transcription factor E3 (TFE3) is reported to be a crucial gene that regulates autophagy flux and lysosome function. Therefore, we investigated the role of TFE3 in a cell model [...] Read more.
Autophagy flux deficiency is closely related to the development of hepatic steatosis. Transcription factor E3 (TFE3) is reported to be a crucial gene that regulates autophagy flux and lysosome function. Therefore, we investigated the role of TFE3 in a cell model of hepatic steatosis. We constructed L02 hepatocyte lines that stably over-expressed or knocked down the expression of TFE3. Subsequently, the effects of TFE3 on hepatocellular lipid metabolism were determined by autophagy flux assay, lipid oil red O (ORO) staining, immunofluorescence staining, and mitochondrial β-oxidation assessment. Finally, we analyzed whether peroxisome proliferative activated receptor gamma coactivator 1α (PGC1α) was the potential target gene of TFE3 in the regulation of hepatic steatosis using a chromatin immunoprecipitation (CHIP) assay and a luciferase reporter system. We found that overexpression of TFE3 markedly alleviated hepatocellular steatosis. On the contrary, downregulation of TFE3 resulted in an aggravated steatosis. The mechanistic studies revealed that the TFE3-manipulated regulatory effects on hepatocellular steatosis are dependent on autophagy-induced lipophagy and PGC1α-mediated fatty acid β-oxidation because blocking these pathways with an Atg5 small interfering RNA (siRNA) or PGC1α siRNA dramatically blunted the TFE3-mediated regulation of steatosis. In conclusion, TFE3 gene provides a novel insight into the treatment of hepatic steatosis and other metabolic disease. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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2694 KiB  
Article
Discovery of Dual ETA/ETB Receptor Antagonists from Traditional Chinese Herbs through in Silico and in Vitro Screening
by Xing Wang, Yuxin Zhang, Qing Liu, Zhixin Ai, Yanling Zhang, Yuhong Xiang and Yanjiang Qiao
Int. J. Mol. Sci. 2016, 17(3), 389; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17030389 - 16 Mar 2016
Cited by 13 | Viewed by 6379
Abstract
Endothelin-1 receptors (ETAR and ETBR) act as a pivotal regulator in the biological effects of ET-1 and represent a potential drug target for the treatment of multiple cardiovascular diseases. The purpose of the study is to discover dual ETA/ETB receptor antagonists from traditional [...] Read more.
Endothelin-1 receptors (ETAR and ETBR) act as a pivotal regulator in the biological effects of ET-1 and represent a potential drug target for the treatment of multiple cardiovascular diseases. The purpose of the study is to discover dual ETA/ETB receptor antagonists from traditional Chinese herbs. Ligand- and structure-based virtual screening was performed to screen an in-house database of traditional Chinese herbs, followed by a series of in vitro bioassay evaluation. Aristolochic acid A (AAA) was first confirmed to be a dual ETA/ETB receptor antagonist based intracellular calcium influx assay and impedance-based assay. Dose-response curves showed that AAA can block both ETAR and ETBR with IC50 of 7.91 and 7.40 μM, respectively. Target specificity and cytotoxicity bioassay proved that AAA is a selective dual ETA/ETB receptor antagonist and has no significant cytotoxicity on HEK293/ETAR and HEK293/ETBR cells within 24 h. It is a feasible and effective approach to discover bioactive compounds from traditional Chinese herbs using in silico screening combined with in vitro bioassay evaluation. The structural characteristic of AAA for its activity was especially interpreted, which could provide valuable reference for the further structural modification of AAA. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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1268 KiB  
Article
In Silico Screening Identifies a Novel Potential PARP1 Inhibitor Targeting Synthetic Lethality in Cancer Treatment
by Jian Li, Nan Zhou, Peiling Cai and Jinku Bao
Int. J. Mol. Sci. 2016, 17(2), 258; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17020258 - 19 Feb 2016
Cited by 25 | Viewed by 6626
Abstract
Synthetic lethality describes situations in which defects in two different genes or pathways together result in cell death. This concept has been applied to drug development for cancer treatment, as represented by Poly (ADP-ribose) polymerase (PARPs) inhibitors. In the current study, we performed [...] Read more.
Synthetic lethality describes situations in which defects in two different genes or pathways together result in cell death. This concept has been applied to drug development for cancer treatment, as represented by Poly (ADP-ribose) polymerase (PARPs) inhibitors. In the current study, we performed a computational screening to discover new PARP inhibitors. Among the 11,247 compounds analyzed, one natural product, ZINC67913374, stood out by its superior performance in the simulation analyses. Compared with the FDA approved PARP1 inhibitor, olaparib, our results demonstrated that the ZINC67913374 compound achieved a better grid score (−86.8) and amber score (−51.42). Molecular dynamics simulations suggested that the PARP1-ZINC67913374 complex was more stable than olaparib. The binding free energy for ZINC67913374 was −177.28 kJ/mol while that of olaparib was −159.16 kJ/mol. These results indicated ZINC67913374 bound to PARP1 with a higher affinity, which suggest ZINC67913374 has promising potential for cancer drug development. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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6117 KiB  
Article
Icaritin Inhibits Collagen Degradation-Related Factors and Facilitates Collagen Accumulation in Atherosclerotic Lesions: A Potential Action for Plaque Stabilization
by Zong-Kang Zhang, Jie Li, De-Xin Yan, Wing-Nang Leung and Bao-Ting Zhang
Int. J. Mol. Sci. 2016, 17(2), 169; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17020169 - 28 Jan 2016
Cited by 17 | Viewed by 5349
Abstract
Most acute coronary syndromes result from rupture of vulnerable atherosclerotic plaques. The collagen content of plaques may critically affect plaque stability. This study tested whether Icaritin (ICT), an intestinal metabolite of Epimedium-derived flavonoids, could alter the collagen synthesis/degradation balance in atherosclerotic lesions. Rabbits [...] Read more.
Most acute coronary syndromes result from rupture of vulnerable atherosclerotic plaques. The collagen content of plaques may critically affect plaque stability. This study tested whether Icaritin (ICT), an intestinal metabolite of Epimedium-derived flavonoids, could alter the collagen synthesis/degradation balance in atherosclerotic lesions. Rabbits were fed with an atherogenic diet for four months. Oral administration of ICT (10 mg·kg−1·day−1) was started after two months of an atherogenic diet and lasted for two months. The collagen degradation-related parameters, including macrophages accumulation, content and activity of interstitial collagenase-1 (MMP-1), and the collagen synthesis-related parameters, including amount and distribution of smooth muscle cells (SMC) and collagen mRNA/protein levels, were evaluated in the aorta. ICT reduced plasma lipid levels, inhibited macrophage accumulation, lowered MMP-1 mRNA and protein expression, and suppressed proteolytic activity of pro-MMP-1 and MMP-1 in the aorta. ICT changed the distribution of the SMCs towards the fibrous cap of lesions without increasing the amount of SMCs. Higher collagen protein content in lesions and aorta homogenates was observed with ICT treatment compared with the atherogenic diet only, without altered collagen mRNA level. These results suggest that ICT could inhibit the collagen degradation-related factors and facilitate collagen accumulation in atherosclerotic lesions, indicating a new potential of ICT in atherosclerotic plaques. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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3813 KiB  
Article
The Protective Effect of Icariin on Mitochondrial Transport and Distribution in Primary Hippocampal Neurons from 3× Tg-AD Mice
by Yijing Chen, Shuangxue Han, Xiuxian Huang, Jiazuan Ni and Xiaoyang He
Int. J. Mol. Sci. 2016, 17(2), 163; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17020163 - 27 Jan 2016
Cited by 31 | Viewed by 6143
Abstract
Icariin, a pharmacologically active component isolated from the Chinese herb Epimedium, has been shown to improve spatial learning and memory abilities in Alzheimer’s disease (AD) rats through inhibition of Aβ production and tau protein hyperphosphorylation. However, the potential mechanism of icariin-induced protective effects [...] Read more.
Icariin, a pharmacologically active component isolated from the Chinese herb Epimedium, has been shown to improve spatial learning and memory abilities in Alzheimer’s disease (AD) rats through inhibition of Aβ production and tau protein hyperphosphorylation. However, the potential mechanism of icariin-induced protective effects against mitochondrial dysfunctions in AD still remains unclear. In the present study, we investigated the effect of icariin on the modulation of mitochondrial transport and distribution in primary hippocampal cultures from triple-transgenic (3× Tg) AD mice. The results showed that icariin enhanced mitochondrial motility and increased mitochondrial index and mitochondrial length and size in the diseased neurons. Additionally, the expression of the key mitochondrial enzyme, pyruvate dehydrogenase-E1α (PDHE1α), and the post synaptic density protein 95 (PSD95), was preserved in AD neurons after icariin treatment, accompanied by a downregulation of Aβ and phosphorylated tau expression in the corresponding areas. Further study showed that icariin treatment resulted in a decrease in mitochondrial fission protein dynamin-related protein 1 (Drp1) and an increase in fusion protein Mitofusin 2 (Mfn2). These data indicate that icariin can promote mitochondrial transport, protect mitochondria against fragmentation and preserve the expression of mitochondrial and synaptic functional proteins in AD neurons. Thus, icariin may be a potential therapeutic complement for AD and other mitochondrial malfunction-related neuronal degenerative diseases. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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2532 KiB  
Article
The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice
by Qun Zhao, Min Yang, Yanping Deng, Haitao Yu, Linlin Wang, Fukang Teng, Kenka Cho, Hongmei Ma, Peng Wu, Xue Li, Wanying Wu, Xuan Liu, Feng Xu, Baohong Jiang and De-An Guo
Int. J. Mol. Sci. 2015, 16(12), 29345-29356; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161226176 - 09 Dec 2015
Cited by 23 | Viewed by 5818
Abstract
Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine [...] Read more.
Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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2331 KiB  
Article
Henrin A: A New Anti-HIV Ent-Kaurane Diterpene from Pteris henryi
by Wan-Fei Li, Juan Wang, Jing-Jie Zhang, Xun Song, Chuen-Fai Ku, Juan Zou, Ji-Xin Li, Li-Jun Rong, Lu-Tai Pan and Hong-Jie Zhang
Int. J. Mol. Sci. 2015, 16(11), 27978-27987; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161126071 - 24 Nov 2015
Cited by 16 | Viewed by 6372
Abstract
Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by [...] Read more.
Henrin A (1), a new ent-kaurane diterpene, was isolated from the leaves of Pteris henryi. The chemical structure was elucidated by analysis of the spectroscopic data including one-dimensional (1D) and two-dimensional (2D) NMR spectra, and was further confirmed by X-ray crystallographic analysis. The compound was evaluated for its biological activities against a panel of cancer cell lines, dental bacterial biofilm formation, and HIV. It displayed anti-HIV potential with an IC50 value of 9.1 µM (SI = 12.2). Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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2972 KiB  
Article
Andrographolide Inhibits Ovariectomy-Induced Bone Loss via the Suppression of RANKL Signaling Pathways
by Tao Wang, Qian Liu, Lin Zhou, Jin Bo Yuan, Xixi Lin, Rong Zeng, Xiaonan Liang, Jinmin Zhao and Jiake Xu
Int. J. Mol. Sci. 2015, 16(11), 27470-27481; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161126039 - 17 Nov 2015
Cited by 16 | Viewed by 5706
Abstract
Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP), a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect [...] Read more.
Osteoporosis is a debilitating skeletal disorder with an increased risk of low-energy fracture, which commonly occurs among postmenopausal women. Andrographolide (AP), a natural product isolated from Andrographis paniculata, has been found to have anti-inflammatory, anti-cancer, anti-asthmatic, and neuro-protective properties. However, its therapeutic effect on osteoporosis is unknown. In this study, an ovariectomy (OVX) mouse model was used to evaluate the therapeutic effects of AP on post-menopausal osteoporosis by using micro-computed tomography (micro-CT). Bone marrow-derived osteoclast culture was used to examine the inhibitory effect of AP on osteoclastogenesis. Real time PCR was employed to examine the effect of AP on the expression of osteoclast marker genes. The activities of transcriptional factors NF-κB and NFATc1 were evaluated using a luciferase reporter assay, and the IκBα protein level was analyzed by Western blot. We found that OVX mice treated with AP have greater bone volume (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) compared to vehicle-treated OVX mice. AP inhibited RANKL-induced osteoclastogenesis, the expression of osteoclast marker genes including cathepsin K (Ctsk), TRACP (Acp5), and NFATc1, as well as the transcriptional activities of NF-κB and NFATc1. In conclusion, our results suggest that AP inhibits estrogen deficiency-induced bone loss in mice via the suppression of RANKL-induced osteoclastogensis and NF-κB and NFATc1 activities and, thus, might have therapeutic potential for osteoporosis. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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2678 KiB  
Article
Berberine Sulfate Attenuates Osteoclast Differentiation through RANKL Induced NF-κB and NFAT Pathways
by Lin Zhou, Fangming Song, Qian Liu, Mingli Yang, Jinmin Zhao, Renxiang Tan, Jun Xu, Ge Zhang, Julian M. W. Quinn, Jennifer Tickner and Jiake Xu
Int. J. Mol. Sci. 2015, 16(11), 27087-27096; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161125998 - 13 Nov 2015
Cited by 26 | Viewed by 6113
Abstract
Osteoporosis, a metabolic bone disease, is characterized by an excessive formation and activation of osteoclasts. Anti-catabolic treatment using natural compounds has been proposed as a potential therapeutic strategy against the osteoclast related osteolytic diseases. In this study, the activity of berberine sulfate (an [...] Read more.
Osteoporosis, a metabolic bone disease, is characterized by an excessive formation and activation of osteoclasts. Anti-catabolic treatment using natural compounds has been proposed as a potential therapeutic strategy against the osteoclast related osteolytic diseases. In this study, the activity of berberine sulfate (an orally available form of berberine) on osteoclast differentiation and its underlying molecular mechanisms of action were investigated. Using bone marrow macrophages (BMMs) derived osteoclast culture system, we showed that berberine sulfate at the dose of 0.25, 0.5 and 1 μM significantly inhibited the formation of osteoclasts. Notably, berberine sulfate at these doses did not affect the BMM viability. In addition, we observed that berberine sulfate inhibited the expression of osteoclast marker genes, including cathepsin K (Ctsk), nuclear factor of activated T cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP, Acp5) and Vacuolar-type H+-ATPase V0 subunit D2 (V-ATPase d2). Luciferase reporter gene assay and Western blot analysis further revealed that berberine sulfate inhibits receptor for activation of nuclear factor ligand (RANKL)-induced NF-κB and NFAT activity. Taken together, our results suggest that berberine sulfate is a natural compound potentially useful for the treatment of osteoporosis. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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1359 KiB  
Article
Natural Germacrane Sesquiterpenes Inhibit Osteoclast Formation, Bone Resorption, RANKL-Induced NF-κB Activation, and IκBα Degradation
by Shengnan Qin, Estabelle Ang, Libing Dai, Xiaohong Yang, Dongping Ye, Honghui Chen, Lin Zhou, Mingli Yang, Dian Teguh, Renxiang Tan, Jun Xu, Jennifer Tickner, Nathan J. Pavlos and Jiake Xu
Int. J. Mol. Sci. 2015, 16(11), 26599-26607; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161125972 - 05 Nov 2015
Cited by 13 | Viewed by 5364
Abstract
Osteolytic bone diseases are commonly presented with enhanced osteoclast formation and bone resorption. Sesquiterpene lactone natural compounds have been found to possess anti-inflammatory and immune-modulation effects. Here, we identified three germacrane sesquiterpenes using computer-based virtual screening for the structural similarity with sesquiterpene lactone, [...] Read more.
Osteolytic bone diseases are commonly presented with enhanced osteoclast formation and bone resorption. Sesquiterpene lactone natural compounds have been found to possess anti-inflammatory and immune-modulation effects. Here, we identified three germacrane sesquiterpenes using computer-based virtual screening for the structural similarity with sesquiterpene lactone, parthenolide. We showed that natural germacrane sesquiterpene compounds A, B, and C inhibit osteoclast formation and bone resorption in a dose-dependent manner, with relative potency compound A > compound C > compound B based on their equimolar concentrations. Mechanistic studies by Luciferase reporter gene assay and Western blot analysis showed that germacrane sesquiterpene compound A inhibits RANKL-induced activation of NF-κB and IκBα degradation. This study reveals that natural germacrane sesquiterpene compounds are inhibitors for osteoclast formation and bone resorption, and provides evidence that naturally-occurring compounds might be beneficial as alternative medicine for the prevention and treatment of osteolysis. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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Article
Improved Chemotherapeutic Activity by Morus alba Fruits through Immune Response of Toll-Like Receptor 4
by Bo Yoon Chang, Seon Beom Kim, Mi Kyeong Lee, Hyun Park and Sung Yeon Kim
Int. J. Mol. Sci. 2015, 16(10), 24139-24158; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161024139 - 13 Oct 2015
Cited by 25 | Viewed by 6653
Abstract
Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of [...] Read more.
Morus alba L. fruits have long been used in traditional medicine by many cultures. Their medicinal attributes include cardiovascular, hepatoprotective, neuroprotective and immunomodulatory actions. However, their mechanism of macrophage activation and anti-cancer effects remain unclear. The present study investigated the molecular mechanisms of immune stimulation and improved chemotherapeutic effect of M. alba L. fruit extract (MFE). MFE stimulated the production of cytokines, nitric oxide (NO) and tumor necrosis factor-α (TNF-α) and tumoricidal properties of macrophages. MFE activated macrophages through the mitogen-activated protein kinase (MAPKinase) and nuclear factor-κB (NF-κB) signaling pathways downstream from toll-like receptor (TLR) 4. MFE was shown to exhibit cytotoxicity of CT26 cells via the activated macrophages, even though MFE did not directly affect CT26 cells. In a xenograft mouse model, MFE significantly enhanced anti-cancer activity combined with 5-fluorouracil and markedly promoted splenocyte proliferation, natural killer (NK) cell activity, cytotoxic T lymphocyte (CTL) activity and IFN-γ production. Immunoglobulin G (IgG) antibody levels were significantly increased. These results indicate the indirect anti-cancer activity of MFE through improved immune response mediated by TLR4 signaling. M. alba L. fruit extract might be a potential anti-tumor immunomodulatory candidate chemotherapy agent. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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Review

Jump to: Research

3208 KiB  
Review
Molecular Mechanisms and Translational Therapies for Human Epidermal Receptor 2 Positive Breast Cancer
by Quanxia Lv, Ziyuan Meng, Yuanyuan Yu, Feng Jiang, Daogang Guan, Chao Liang, Junwei Zhou, Aiping Lu and Ge Zhang
Int. J. Mol. Sci. 2016, 17(12), 2095; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17122095 - 14 Dec 2016
Cited by 36 | Viewed by 14446
Abstract
Breast cancer is the second leading cause of cancer death among women. Human epidermal receptor 2 (HER2) positive breast cancer (HER2+ BC) is the most aggressive subtype of breast cancer, with poor prognosis and a high rate of recurrence. About one third of [...] Read more.
Breast cancer is the second leading cause of cancer death among women. Human epidermal receptor 2 (HER2) positive breast cancer (HER2+ BC) is the most aggressive subtype of breast cancer, with poor prognosis and a high rate of recurrence. About one third of breast cancer is HER2+ BC with significantly high expression level of HER2 protein compared to other subtypes. Therefore, HER2 is an important biomarker and an ideal target for developing therapeutic strategies for the treatment HER2+ BC. In this review, HER2 structure and physiological and pathological roles in HER2+ BC are discussed. Two diagnostic tests, immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH), for evaluating HER2 expression levels are briefly introduced. The current mainstay targeted therapies for HER2+ BC include monoclonal antibodies, small molecule tyrosine kinase inhibitors, antibody–drug conjugates (ADC) and other emerging anti-HER2 agents. In clinical practice, combination therapies are commonly adopted in order to achieve synergistic drug response. This review will help to better understand the molecular mechanism of HER2+ BC and further facilitate the development of more effective therapeutic strategies against HER2+ BC. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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3768 KiB  
Review
Roles of d-Amino Acids on the Bioactivity of Host Defense Peptides
by Hao Li, Nuttapat Anuwongcharoen, Aijaz Ahmad Malik, Virapong Prachayasittikul, Jarl E. S. Wikberg and Chanin Nantasenamat
Int. J. Mol. Sci. 2016, 17(7), 1023; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17071023 - 30 Jun 2016
Cited by 63 | Viewed by 8988
Abstract
Host defense peptides (HDPs) are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next generation of broad spectrum therapeutic agents effective against a vast array of pathogens and tumor. As such, many approaches have [...] Read more.
Host defense peptides (HDPs) are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next generation of broad spectrum therapeutic agents effective against a vast array of pathogens and tumor. As such, many approaches have been taken to improve the therapeutic efficacy of HDPs. Amongst these methods, the incorporation of d-amino acids (d-AA) is an approach that has demonstrated consistent success in improving HDPs. Although, virtually all HDP review articles briefly mentioned about the role of d-AA, however it is rather surprising that no systematic review specifically dedicated to this topic exists. Given the impact that d-AA incorporation has on HDPs, this review aims to fill that void with a systematic discussion of the impact of d-AA on HDPs. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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9224 KiB  
Review
Recent Advances in Developing Small Molecules Targeting Nucleic Acid
by Maolin Wang, Yuanyuan Yu, Chao Liang, Aiping Lu and Ge Zhang
Int. J. Mol. Sci. 2016, 17(6), 779; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17060779 - 30 May 2016
Cited by 66 | Viewed by 8251
Abstract
Nucleic acids participate in a large number of biological processes. However, current approaches for small molecules targeting protein are incompatible with nucleic acids. On the other hand, the lack of crystallization of nucleic acid is the limiting factor for nucleic acid drug design. [...] Read more.
Nucleic acids participate in a large number of biological processes. However, current approaches for small molecules targeting protein are incompatible with nucleic acids. On the other hand, the lack of crystallization of nucleic acid is the limiting factor for nucleic acid drug design. Because of the improvements in crystallization in recent years, a great many structures of nucleic acids have been reported, providing basic information for nucleic acid drug discovery. This review focuses on the discovery and development of small molecules targeting nucleic acids. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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576 KiB  
Review
Targeted Delivery Systems for Molecular Therapy in Skeletal Disorders
by Lei Dang, Jin Liu, Fangfei Li, Luyao Wang, Defang Li, Baosheng Guo, Xiaojuan He, Feng Jiang, Chao Liang, Biao Liu, Shaikh Atik Badshah, Bing He, Jun Lu, Cheng Lu, Aiping Lu and Ge Zhang
Int. J. Mol. Sci. 2016, 17(3), 428; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17030428 - 22 Mar 2016
Cited by 36 | Viewed by 6627
Abstract
Abnormalities in the integral components of bone, including bone matrix, bone mineral and bone cells, give rise to complex disturbances of skeletal development, growth and homeostasis. Non-specific drug delivery using high-dose systemic administration may decrease therapeutic efficacy of drugs and increase the risk [...] Read more.
Abnormalities in the integral components of bone, including bone matrix, bone mineral and bone cells, give rise to complex disturbances of skeletal development, growth and homeostasis. Non-specific drug delivery using high-dose systemic administration may decrease therapeutic efficacy of drugs and increase the risk of toxic effects in non-skeletal tissues, which remain clinical challenges in the treatment of skeletal disorders. Thus, targeted delivery systems are urgently needed to achieve higher drug delivery efficiency, improve therapeutic efficacy in the targeted cells/tissues, and minimize toxicities in non-targeted cells/tissues. In this review, we summarize recent progress in the application of different targeting moieties and nanoparticles for targeted drug delivery in skeletal disorders, and also discuss the advantages, challenges and perspectives in their clinical translation. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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1482 KiB  
Review
Molecular Selection, Modification and Development of Therapeutic Oligonucleotide Aptamers
by Yuanyuan Yu, Chao Liang, Quanxia Lv, Defang Li, Xuegong Xu, Baoqin Liu, Aiping Lu and Ge Zhang
Int. J. Mol. Sci. 2016, 17(3), 358; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17030358 - 11 Mar 2016
Cited by 50 | Viewed by 7529
Abstract
Monoclonal antibodies are the dominant agents used in inhibition of biological target molecules for disease therapeutics, but there are concerns of immunogenicity, production, cost and stability. Oligonucleotide aptamers have comparable affinity and specificity to targets with monoclonal antibodies whilst they have minimal immunogenicity, [...] Read more.
Monoclonal antibodies are the dominant agents used in inhibition of biological target molecules for disease therapeutics, but there are concerns of immunogenicity, production, cost and stability. Oligonucleotide aptamers have comparable affinity and specificity to targets with monoclonal antibodies whilst they have minimal immunogenicity, high production, low cost and high stability, thus are promising inhibitors to rival antibodies for disease therapy. In this review, we will compare the detailed advantages and disadvantages of antibodies and aptamers in therapeutic applications and summarize recent progress in aptamer selection and modification approaches. We will present therapeutic oligonucleotide aptamers in preclinical studies for skeletal diseases and further discuss oligonucleotide aptamers in different stages of clinical evaluation for various disease therapies including macular degeneration, cancer, inflammation and coagulation to highlight the bright commercial future and potential challenges of therapeutic oligonucleotide aptamers. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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819 KiB  
Review
Withaferin-A—A Natural Anticancer Agent with Pleitropic Mechanisms of Action
by In-Chul Lee and Bu Young Choi
Int. J. Mol. Sci. 2016, 17(3), 290; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17030290 - 04 Mar 2016
Cited by 120 | Viewed by 10915
Abstract
Cancer, being the second leading cause of mortality, exists as a formidable health challenge. In spite of our enormous efforts, the emerging complexities in the molecular nature of disease progression limit the real success in finding an effective cancer cure. It is now [...] Read more.
Cancer, being the second leading cause of mortality, exists as a formidable health challenge. In spite of our enormous efforts, the emerging complexities in the molecular nature of disease progression limit the real success in finding an effective cancer cure. It is now conceivable that cancer is, in fact, a progressive illness, and the morbidity and mortality from cancer can be reduced by interfering with various oncogenic signaling pathways. A wide variety of structurally diverse classes of bioactive phytochemicals have been shown to exert anticancer effects in a large number of preclinical studies. Multiple lines of evidence suggest that withaferin-A can prevent the development of cancers of various histotypes. Accumulating data from different rodent models and cell culture experiments have revealed that withaferin-A suppresses experimentally induced carcinogenesis, largely by virtue of its potent anti-oxidative, anti-inflammatory, anti-proliferative and apoptosis-inducing properties. Moreover, withaferin-A sensitizes resistant cancer cells to existing chemotherapeutic agents. The purpose of this review is to highlight the mechanistic aspects underlying anticancer effects of withaferin-A. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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1195 KiB  
Review
Innovative Target Therapies Are Able to Block the Inflammation Associated with Dysfunction of the Cholesterol Biosynthesis Pathway
by Annalisa Marcuzzi, Elisa Piscianz, Claudia Loganes, Liza Vecchi Brumatti, Alessandra Knowles, Sabrine Bilel, Alberto Tommasini, Roberta Bortul and Marina Zweyer
Int. J. Mol. Sci. 2016, 17(1), 47; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17010047 - 30 Dec 2015
Cited by 7 | Viewed by 6885
Abstract
The cholesterol pathway is an essential biochemical process aimed at the synthesis of bioactive molecules involved in multiple crucial cellular functions. The end products of this pathway are sterols, such as cholesterol, which are essential components of cell membranes, precursors of steroid hormones, [...] Read more.
The cholesterol pathway is an essential biochemical process aimed at the synthesis of bioactive molecules involved in multiple crucial cellular functions. The end products of this pathway are sterols, such as cholesterol, which are essential components of cell membranes, precursors of steroid hormones, bile acids and other molecules such as ubiquinone. Several diseases are caused by defects in this metabolic pathway: the most severe forms of which cause neurological involvement (psychomotor retardation and cerebellar ataxia) as a result of a variety of cellular impairments, including mitochondrial dysfunction. These pathologies are induced by convergent mechanisms in which the mitochondrial unit plays a pivotal role contributing to defective apoptosis, autophagy and mitophagy processes. Unraveling these mechanisms would contribute to the development of effective drug treatments for these disorders. In addition, the development of biochemical models could have a substantial impact on the understanding of the mechanism of action of drugs that act on this pathway in multifactor disorders. In this review we will focus in particular on inhibitors of cholesterol synthesis, mitochondria-targeted drugs and inhibitors of the inflammasome. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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788 KiB  
Review
Exploring Different Strategies for Efficient Delivery of Colorectal Cancer Therapy
by Congcong Lin, Huei Leng Helena Ng, Weisan Pan, Hubiao Chen, Ge Zhang, Zhaoxiang Bian, Aiping Lu and Zhijun Yang
Int. J. Mol. Sci. 2015, 16(11), 26936-26952; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161125995 - 11 Nov 2015
Cited by 32 | Viewed by 7450
Abstract
Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death in the world. Currently available chemotherapy of CRC usually delivers the drug to both normal as well as cancerous tissues, thus leading to numerous undesirable effects. [...] Read more.
Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer death in the world. Currently available chemotherapy of CRC usually delivers the drug to both normal as well as cancerous tissues, thus leading to numerous undesirable effects. Much emphasis is being laid on the development of effective drug delivery systems for achieving selective delivery of the active moiety at the anticipated site of action with minimized unwanted side effects. Researchers have employed various techniques (dependent on pH, time, pressure and/or bacteria) for targeting drugs directly to the colonic region. On the other hand, systemic drug delivery strategies to specific molecular targets (such as FGFR, EGFR, CD44, EpCAM, CA IX, PPARγ and COX-2) overexpressed by cancerous cells have also been shown to be effective. This review aims to put forth an overview of drug delivery technologies that have been, and may be developed, for the treatment of CRC. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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2176 KiB  
Review
Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems
by Feng Jiang, Biao Liu, Jun Lu, Fangfei Li, Defang Li, Chao Liang, Lei Dang, Jin Liu, Bing He, Shaikh Atik Badshah, Cheng Lu, Xiaojuan He, Baosheng Guo, Xiao-Bing Zhang, Weihong Tan, Aiping Lu and Ge Zhang
Int. J. Mol. Sci. 2015, 16(10), 23784-23822; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms161023784 - 09 Oct 2015
Cited by 75 | Viewed by 11242
Abstract
Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing [...] Read more.
Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems. Full article
(This article belongs to the Special Issue Molecule- and Cell-Targeted Drug Design and Screening and Identification of Natural Product)
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