Novel Nanobiotechnologies for the Discovery and Delivery of Anti-cancer Drugs

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 56709

Special Issue Editor


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Guest Editor
Department of Biomedical Engineering, School of Integrative Engineering, College of ICT Engineering, Chung-Ang University, Seoul 06974, Republic of Korea
Interests: nanomedicine; biosensor; theragnostics; drug delivery; nanobiomaterials
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Special Issue Information

Dear Colleagues,

New nanobiotechnologies are emerging for the discovery and delivery of anticancer drugs. Among the many candidate anti-cancer drugs, the technology to quickly select and effectively delivery targets that are expected to have sufficient therapeutic efficacy is critical. Therefore, the requirement for high-throughput screening and analyses of anti-cancer drugs has become increasingly relevant. At the same time, the new tools and carriers developed from nanobiotechnologies delivering anti-cancer drugs to the target tumor have also been significantly employed. Achievement of these goals requires a detailed study of the single cell assays, drug-screening technologies, drug efficacy tests, drug-delivery tools, and characterization of pharmaco-dynamics and -kinetics.  

This Special Issue will highlight the current state-of-the-art of high-throughput screening tools for the discovery and characterization of anti-cancer drugs, as well as the most up-to-date nanobiotechnologies for the effective delivery of drug molecules. These methods would also suggest prospects for optimizing cancer therapies. Towards these aims, this Special Issue will compile a series of research articles and review papers dedicated to the development of drug screening methods, drug discovery tools, the drug delivery approaches, and to the use of these methods to improve the anti-cancer drug efficacy.

Prof. Jonghoon Choi
Guest Editor

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Published Papers (13 papers)

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Research

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17 pages, 2917 KiB  
Article
Detection of Lysyl Oxidase Activity in Tumor Extracellular Matrix Using Peptide-Functionalized Gold Nanoprobes
by Han Young Kim, Mihee Jo, Ju A La, Youngjin Choi, Eun Chul Cho, Su Hee Kim, Youngmee Jung, Kwangmeyung Kim and Ju Hee Ryu
Cancers 2021, 13(18), 4523; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13184523 - 08 Sep 2021
Cited by 4 | Viewed by 2198
Abstract
High LOX levels in the tumor microenvironment causes the cross-linking of extracellular matrix components and increases the stiffness of tumor tissue. Thus, LOX plays an important role in tumorigenesis and in lowering the tumor response to anticancer drugs. Despite comprehensive efforts to identify [...] Read more.
High LOX levels in the tumor microenvironment causes the cross-linking of extracellular matrix components and increases the stiffness of tumor tissue. Thus, LOX plays an important role in tumorigenesis and in lowering the tumor response to anticancer drugs. Despite comprehensive efforts to identify the roles of LOX in the tumor microenvironment, sensitive and accurate detection methods have not yet been established. Here, we suggest the use of gold nanoparticles functionalized with LOX-sensitive peptides (LS-AuNPs) that aggregate upon exposure to LOX, resulting in a visual color change. LOX-sensitive peptides (LS-peptides) contain lysine residues that are converted to allysine in the presence of LOX, which is highly reactive and binds to adjacent allysine, resulting in the aggregation of the AuNPs. We demonstrated that the synthesized LS-AuNPs are capable of detecting LOX sensitively, specifically both in vitro and in the tissue extract. Moreover, the suggested LS-AuNP-based assay is more sensitive than commonly employed assays or commercially available kits. Therefore, the LS-AuNPs developed in this study can be used to detect LOX levels and can be further used to predict the stiffness or the anticancer drug resistance of the tumor. Full article
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17 pages, 3046 KiB  
Article
Three-Dimensional Vascularized Lung Cancer-on-a-Chip with Lung Extracellular Matrix Hydrogels for In Vitro Screening
by Sangun Park, Tae Hee Kim, Soo Hyun Kim, Seungkwon You and Youngmee Jung
Cancers 2021, 13(16), 3930; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13163930 - 05 Aug 2021
Cited by 32 | Viewed by 3374
Abstract
Recent advances in immunotherapies and molecularly targeted therapies have led to an increased interest in exploring the field of in vitro tumor mimetic platforms. An increasing need to understand the mechanisms of anti-cancer therapies has led to the development of natural tumor tissue-like [...] Read more.
Recent advances in immunotherapies and molecularly targeted therapies have led to an increased interest in exploring the field of in vitro tumor mimetic platforms. An increasing need to understand the mechanisms of anti-cancer therapies has led to the development of natural tumor tissue-like in vitro platforms capable of simulating the tumor microenvironment. The incorporation of vascular structures into the in vitro platforms could be a crucial factor for functional investigation of most anti-cancer therapies, including immunotherapies, which are closely related to the circulatory system. Decellularized lung extracellular matrix (ldECM), comprised of ECM components and pro-angiogenic factors, can initiate vascularization and is ideal for mimicking the natural microenvironment. In this study, we used a ldECM-based hydrogel to develop a 3D vascularized lung cancer-on-a-chip (VLCC). We specifically encapsulated tri-cellular spheroids made from A549 cells, HUVECs, and human lung fibroblasts, for simulating solid type lung cancer. Additionally, two channels were incorporated in the hydrogel construct to mimic perfusable vessel structures that resemble arterioles or venules. Our study highlights how a more effective dose-dependent action of the anti-cancer drug Doxorubicin was observed using a VLCC over 2D screening. This observation confirmed the potential of the VLCC as a 3D in vitro drug screening tool. Full article
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25 pages, 5726 KiB  
Article
Co-Delivery of CPT-11 and Panobinostat with Anti-GD2 Antibody Conjugated Immunoliposomes for Targeted Combination Chemotherapy
by Gils Jose, Yu-Jen Lu, Jung-Tung Hung, Alice L. Yu and Jyh-Ping Chen
Cancers 2020, 12(11), 3211; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113211 - 31 Oct 2020
Cited by 22 | Viewed by 3273
Abstract
The consistent expression of disialoganglioside GD2 in neuroblastoma tumor cells and its restricted expression in normal tissues open the possibility to use it for molecularly targeted neuroblastoma therapy. On the other hand, immunoliposomes combining antibody-mediated tumor recognition with liposomal delivery of chemotherapeutics have [...] Read more.
The consistent expression of disialoganglioside GD2 in neuroblastoma tumor cells and its restricted expression in normal tissues open the possibility to use it for molecularly targeted neuroblastoma therapy. On the other hand, immunoliposomes combining antibody-mediated tumor recognition with liposomal delivery of chemotherapeutics have been proved to enhance therapeutic efficacy in brain tumors. Therefore, we develop immunoliposomes (ImmuLipCP) conjugated with anti-GD2 antibody, for targeted co-delivery of CPT-11 and panobinostat in this study. U87MG human glioma cell line and its drug resistant variant (U87DR), which were confirmed to be associated with low and high expression of cell surface GD2, were employed to compare the targeting efficacy. From in vitro cytotoxicity assay, CPT-11 showed synergism drug interaction with panobinostat to support co-delivery of both drugs with ImmuLipCP for targeted synergistic combination chemotherapy. The molecular targeting mechanism was elucidated from intracellular uptake efficacy by confocal microscopy and flow cytometry analysis, where 6-fold increase in liposome and 1.8-fold increase in drug uptake efficiency was found using targeted liposomes. This enhanced intracellular trafficking for drug delivery endows ImmuLipCP with pronounced cytotoxicity toward U87DR cells in vitro, with 1.6-fold increase of apoptosis rate. Using xenograft nude mice model with subcutaneously implanted U87DR cells, we observe similar biodistribution profile but 5.1 times higher accumulation rate of ImmuLip from in vivo imaging system (IVIS) observation of Cy5.5-labelled liposomes. Taking advantage of this highly efficient GD-2 targeting, ImmuLipCP was demonstrated to be an effective cancer treatment modality to significantly enhance the anti-cancer therapeutic efficacy in U87DR tumors, shown from the significant reduced tumor size in and prolonged survival time of experiment animals as well as diminished expression of cell proliferation and enhanced expression of apoptosis marker proteins in tumor section. Full article
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15 pages, 2376 KiB  
Article
Combination of Irreversible Electroporation and STING Agonist for Effective Cancer Immunotherapy
by Eun-Jin Go, Hannah Yang, Hong Jae Chon, DaSom Yang, WonHyoung Ryu, Dong-Hyun Kim, Dong Keun Han, Chan Kim and Wooram Park
Cancers 2020, 12(11), 3123; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12113123 - 26 Oct 2020
Cited by 31 | Viewed by 5204
Abstract
Recently, cancer immunotherapy has received attention as a viable solution for the treatment of refractory tumors. However, it still has clinical limitations in its treatment efficacy due to inter-patient tumor heterogeneity and immunosuppressive tumor microenvironment (TME). In this study, we demonstrated the triggering [...] Read more.
Recently, cancer immunotherapy has received attention as a viable solution for the treatment of refractory tumors. However, it still has clinical limitations in its treatment efficacy due to inter-patient tumor heterogeneity and immunosuppressive tumor microenvironment (TME). In this study, we demonstrated the triggering of anti-cancer immune responses by a combination of irreversible electroporation (IRE) and a stimulator of interferon genes (STING) agonist. Optimal electrical conditions inducing damage-associated molecular patterns (DAMPs) by immunogenic cell death (ICD) were determined through in vitro 2D and 3D cell experiments. In the in vivo syngeneic lung cancer model, the combination of IRE and STING agonists demonstrated significant tumor growth inhibition. We believe that the combination strategy of IRE and STING agonists has potential for effective cancer immunotherapy. Full article
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14 pages, 3460 KiB  
Article
Studies on the Drug Loading and Release Profiles of Degradable Chitosan-Based Multilayer Films for Anticancer Treatment
by Hyeongdeok Sun, Daheui Choi, Jiwoong Heo, Se Yong Jung and Jinkee Hong
Cancers 2020, 12(3), 593; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12030593 - 05 Mar 2020
Cited by 26 | Viewed by 3733
Abstract
This study demonstrates the possibility of developing a rapidly degradable chitosan-based multilayer film for controlled drug release. The chitosan (CHI)-based multilayer nanofilms were prepared with three different types of anions, hyaluronic acid (HA), alginic acid (ALG) and tannic acid (TA). Taking advantage of [...] Read more.
This study demonstrates the possibility of developing a rapidly degradable chitosan-based multilayer film for controlled drug release. The chitosan (CHI)-based multilayer nanofilms were prepared with three different types of anions, hyaluronic acid (HA), alginic acid (ALG) and tannic acid (TA). Taking advantage of the Layer-by-Layer (LBL) assembly, each multilayer film has different morphology, porosity and thickness depending on their ionic density, molecular structure and the polymer functionality of the building blocks. We loaded drug models such as doxorubicin hydrochloride (DOX), fluorescein isothiocyanate (FITC) and ovalbumin (Ova) into multilayer films and analyzed the drug loading and release profiles in phosphate-buffered saline (PBS) buffer with the same osmolarity and temperature as the human body. Despite the rapid degradation of the multilayer film in a high pH and salt solution, the drug release profile can be controlled by increasing the functional group density, which results in interaction with the drug. In particular, the abundant carboxylate groups in the CHI/HA film increased the loading amount of DOX and decreased rapid drug release. The TA interaction with DOX via electrostatic interaction, hydrogen bonding and hydrophobic interaction showed a sustained drug release profile. These results serve as principles for fabricating a tailored multilayer film for drug delivery application. Full article
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17 pages, 2789 KiB  
Article
Photo-Functionalized Magnetic Nanoparticles as a Nanocarrier of Photodynamic Anticancer Agent for Biomedical Theragnostics
by Ki Chang Nam, Yong Soo Han, Jong-Min Lee, Si Chan Kim, Guangsup Cho and Bong Joo Park
Cancers 2020, 12(3), 571; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12030571 - 01 Mar 2020
Cited by 16 | Viewed by 3385
Abstract
Various theragnostic agents have been devised and developed as cancer treatments; however, existing agents are often limited by their specific functions and complexities. Here, we report multifunctional magnetite (Fe3O4) nanoparticles functionalized with chlorin e6 (Ce6) and folic acid (FA) [...] Read more.
Various theragnostic agents have been devised and developed as cancer treatments; however, existing agents are often limited by their specific functions and complexities. Here, we report multifunctional magnetite (Fe3O4) nanoparticles functionalized with chlorin e6 (Ce6) and folic acid (FA) using a simple fabrication process to be used as theragnostic agents in photodynamic therapy (PDT). The effectiveness of cellular uptake of Fe3O4-Ce6-FA nanoparticles (FCF NPs) and its visualization as well as the photodynamic anticancer activities were evaluated. The mechanism of cancer cell death by the FCF NPs was also verified with qualitative and quantitative methods. Results indicate that FCF NPs have good penetration efficacy, resulting in excellent in vitro fluorescence and magnetic resonance imaging in cancer cells. FCF NPs exhibited promising anticancer activity in an irradiation time- and FCF NPs-dose-dependent manner in various cancer cell lines, leading to apoptotic cell death via morphological changes in cell membrane, nuclear, and DNA damage, and via overexpression of apoptosis-related genes, such as ZFP36L1, CYR61, GADD45G, caspases-2, -3, -9, 10, and -14. This study suggests that FCF NPs may be safely used in cancer therapy via PDT and could be a versatile therapeutic tool and biocompatible theragnostic agent, which may be used in diagnostic imaging. Full article
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12 pages, 3075 KiB  
Article
Effective Delivery of Anti-Cancer Drug Molecules with Shape Transforming Liquid Metal Particles
by Dasom Kim, Jangsun Hwang, Yonghyun Choi, Yejin Kwon, Jaehee Jang, Semi Yoon and Jonghoon Choi
Cancers 2019, 11(11), 1666; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11111666 - 27 Oct 2019
Cited by 35 | Viewed by 4782
Abstract
Liquid metals are being studied intensively because of their potential as a drug delivery system. Eutectic gallium–indium (EGaIn) alloy liquid metals have a low melting point, low toxicity, and excellent tissue permeability. These properties may enable them to be vascular embolic agents that [...] Read more.
Liquid metals are being studied intensively because of their potential as a drug delivery system. Eutectic gallium–indium (EGaIn) alloy liquid metals have a low melting point, low toxicity, and excellent tissue permeability. These properties may enable them to be vascular embolic agents that can be deformed by light or heat. In this study, we developed EGaIn particles that can deliver anticancer drugs to tumor cells in vitro and change their shapes in response to external stimuli. These particles were prepared by sonicating a solution containing EGaIn and amphiphilic lipids. The liquid metal (LM)/amphiphilic lipid (DSPC, 1,2-distearoyl-sn-glycero-3-phosphocholin) particles formed a vehicle for doxorubicin, an anticancer drug, which was released (up to 50%) when the shape of the particles was deformed by light or heat treatment. LM/DSPC particles are non-toxic and LM/DSPC/doxorubicin particles have anticancer effects (resulting in a cell viability of less than 50%). LM/DSPC/doxorubicin particles were also able to mimic blood vessel embolisms by modifying their shape using precisely controlled light and heat in engineered microchannels. The purpose of this study was to examine the potential of EGaIn materials to treat tumor tissues that cannot be removed by surgery. Full article
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19 pages, 5644 KiB  
Article
Functionalized Tobacco Mosaic Virus Coat Protein Monomers and Oligomers as Nanocarriers for Anti-Cancer Peptides
by Coralie Gamper, Caroline Spenlé, Sonia Boscá, Michael van der Heyden, Mathieu Erhardt, Gertraud Orend, Dominique Bagnard and Manfred Heinlein
Cancers 2019, 11(10), 1609; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11101609 - 22 Oct 2019
Cited by 17 | Viewed by 4281
Abstract
Components with self-assembly properties derived from plant viruses provide the opportunity to design biological nanoscaffolds for the ordered display of agents of diverse nature and with complementing functions. With the aim of designing a functionalized nanoscaffold to target cancer, the coat protein (CP) [...] Read more.
Components with self-assembly properties derived from plant viruses provide the opportunity to design biological nanoscaffolds for the ordered display of agents of diverse nature and with complementing functions. With the aim of designing a functionalized nanoscaffold to target cancer, the coat protein (CP) of Tobacco mosaic virus (TMV) was tested as nanocarrier for an insoluble, highly hydrophobic peptide that targets the transmembrane domain of the Neuropilin-1 (NRP1) receptor in cancer cells. The resulting construct CPL-K (CP-linker-“Kill”) binds to NRP1 in cancer cells and disrupts NRP1 complex formation with PlexA1 as well as downstream Akt survival signaling. The application of CPL-K also inhibits angiogenesis and cell migration. CP was also fused to a peptide that targets the extracellular domain of NRP1 and this fusion protein (CPL-F, CP-Linker-“Find”) is shown to bind to cultured cancer cells and to inhibit NRP1-dependent angiogenesis as well. CPL-K and CPL-F maintain their anti-angiogenic properties upon co-assembly to oligomers/nanoparticles together with CPL. The observations show that the CP of TMV can be employed to generate a functionalized nanoparticle with biological activity. Remarkably, fusion to CPL allowed us to solubilize the highly insoluble transmembrane NRP1 peptide and to retain its anti-angiogenic effect. Full article
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17 pages, 2702 KiB  
Article
Anti-Tumor Drug-Loaded Oxygen Nanobubbles for the Degradation of HIF-1α and the Upregulation of Reactive Oxygen Species in Tumor Cells
by Muhammad Saad Khan, Jangsun Hwang, Kyungwoo Lee, Yonghyun Choi, Youngmin Seo, Hojeong Jeon, Jong Wook Hong and Jonghoon Choi
Cancers 2019, 11(10), 1464; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers11101464 - 29 Sep 2019
Cited by 38 | Viewed by 4382
Abstract
Hypoxia is a key concern during the treatment of tumors, and hypoxia-inducible factor 1 alpha (HIF-1α) has been associated with increased tumor resistance to therapeutic modalities. In this study, doxorubicin-loaded oxygen nanobubbles (Dox/ONBs) were synthesized, and the effectiveness of drug delivery to MDA-MB-231 [...] Read more.
Hypoxia is a key concern during the treatment of tumors, and hypoxia-inducible factor 1 alpha (HIF-1α) has been associated with increased tumor resistance to therapeutic modalities. In this study, doxorubicin-loaded oxygen nanobubbles (Dox/ONBs) were synthesized, and the effectiveness of drug delivery to MDA-MB-231 breast cancer and HeLa cells was evaluated. Dox/ONBs were characterized using optical and fluorescence microscopy, and size measurements were performed through nanoparticle tracking analysis (NTA). The working mechanism of Dox was evaluated using reactive oxygen species (ROS) assays, and cellular penetration was assessed with confocal microscopy. Hypoxic conditions were established to assess the effect of Dox/ONBs under hypoxic conditions compared with normoxic conditions. Our results indicate that Dox/ONBs are effective for drug delivery, enhancing oxygen levels, and ROS generation in tumor-derived cell lines. Full article
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Review

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37 pages, 2531 KiB  
Review
Recent Progress of Nanocarrier-Based Therapy for Solid Malignancies
by Qi-Yao Wei, Yan-Ming Xu and Andy T. Y. Lau
Cancers 2020, 12(10), 2783; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12102783 - 28 Sep 2020
Cited by 67 | Viewed by 4754
Abstract
Conventional chemotherapy is still an important option of cancer treatment, but it has poor cell selectivity, severe side effects, and drug resistance. Utilizing nanoparticles (NPs) to improve the therapeutic effect of chemotherapeutic drugs has been highlighted in recent years. Nanotechnology dramatically changed the [...] Read more.
Conventional chemotherapy is still an important option of cancer treatment, but it has poor cell selectivity, severe side effects, and drug resistance. Utilizing nanoparticles (NPs) to improve the therapeutic effect of chemotherapeutic drugs has been highlighted in recent years. Nanotechnology dramatically changed the face of oncology by high loading capacity, less toxicity, targeted delivery of drugs, increased uptake to target sites, and optimized pharmacokinetic patterns of traditional drugs. At present, research is being envisaged in the field of novel nano-pharmaceutical design, such as liposome, polymer NPs, bio-NPs, and inorganic NPs, so as to make chemotherapy effective and long-lasting. Till now, a number of studies have been conducted using a wide range of nanocarriers for the treatment of solid tumors including lung, breast, pancreas, brain, and liver. To provide a reference for the further application of chemodrug-loaded nanoformulations, this review gives an overview of the recent development of nanocarriers, and the updated status of their use in the treatment of several solid tumors. Full article
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38 pages, 3730 KiB  
Review
Two-Dimensional Theranostic Nanomaterials in Cancer Treatment: State of the Art and Perspectives
by Iruthayapandi Selestin Raja, Moon Sung Kang, Ki Su Kim, Yu Jin Jung and Dong-Wook Han
Cancers 2020, 12(6), 1657; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12061657 - 22 Jun 2020
Cited by 17 | Viewed by 3846
Abstract
As the combination of therapies enhances the performance of biocompatible materials in cancer treatment, theranostic therapies are attracting increasing attention rather than individual approaches. In this review, we describe a variety of two-dimensional (2D) theranostic nanomaterials and their efficacy in ablating tumors. Though [...] Read more.
As the combination of therapies enhances the performance of biocompatible materials in cancer treatment, theranostic therapies are attracting increasing attention rather than individual approaches. In this review, we describe a variety of two-dimensional (2D) theranostic nanomaterials and their efficacy in ablating tumors. Though many literature reports are available to demonstrate the potential application of 2D nanomaterials, we have reviewed here cancer-treating therapies based on such multifunctional nanomaterials abstracting the content from literature works which explain both the in vitro and in vivo level of applications. In addition, we have included a discussion about the future direction of 2D nanomaterials in the field of theranostic cancer treatment. Full article
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17 pages, 1805 KiB  
Review
Hyaluronic Acid-Based Theranostic Nanomedicines for Targeted Cancer Therapy
by So Yun Lee, Moon Sung Kang, Woo Yeup Jeong, Dong-Wook Han and Ki Su Kim
Cancers 2020, 12(4), 940; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12040940 - 10 Apr 2020
Cited by 88 | Viewed by 6480
Abstract
Hyaluronic acid (HA) is a natural mucopolysaccharide and has many useful advantages, including biocompatibility, non-immunogenicity, chemical versatility, non-toxicity, biodegradability, and high hydrophilicity. Numerous tumor cells overexpress several receptors that have a high binding affinity for HA, while these receptors are poorly expressed in [...] Read more.
Hyaluronic acid (HA) is a natural mucopolysaccharide and has many useful advantages, including biocompatibility, non-immunogenicity, chemical versatility, non-toxicity, biodegradability, and high hydrophilicity. Numerous tumor cells overexpress several receptors that have a high binding affinity for HA, while these receptors are poorly expressed in normal body cells. HA-based drug delivery carriers can offer improved solubility and stability of anticancer drugs in biological environments and allow for the targeting of cancer treatments. Based on these benefits, HA has been widely investigated as a promising material for developing the advanced clinical cancer therapies in various formulations, including nanoparticles, micelles, liposomes, and hydrogels, combined with other materials. We describe various approaches and findings showing the feasibility of improvement in theragnosis probes through the application of HA. Full article
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33 pages, 5702 KiB  
Review
Microcellular Environmental Regulation of Silver Nanoparticles in Cancer Therapy: A Critical Review
by Ganesan Raja, Yoon-Kwan Jang, Jung-Soo Suh, Heon-Su Kim, Sang Hyun Ahn and Tae-Jin Kim
Cancers 2020, 12(3), 664; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers12030664 - 12 Mar 2020
Cited by 63 | Viewed by 6041
Abstract
Silver nanoparticles (AgNPs) play significant roles in various cancer cells such as functional heterogeneity, microenvironmental differences, and reversible changes in cell properties (e.g., chemotherapy). There is a lack of targets for processes involved in tumor cellular heterogeneity, such as metabolic clampdown, cytotoxicity, and [...] Read more.
Silver nanoparticles (AgNPs) play significant roles in various cancer cells such as functional heterogeneity, microenvironmental differences, and reversible changes in cell properties (e.g., chemotherapy). There is a lack of targets for processes involved in tumor cellular heterogeneity, such as metabolic clampdown, cytotoxicity, and genotoxicity, which hinders microenvironmental biology. Proteogenomics and chemical metabolomics are important tools that can be used to study proteins/genes and metabolites in cells, respectively. Chemical metabolomics have many advantages over genomics, transcriptomics, and proteomics in anticancer therapy. However, recent studies with AgNPs have revealed considerable genomic and proteomic changes, particularly in genes involved in tumor suppression, apoptosis, and oxidative stress. Metabolites interact biochemically with energy storage, neurotransmitters, and antioxidant defense systems. Mechanobiological studies of AgNPs in cancer metabolomics suggest that AgNPs may be promising tools that can be exploited to develop more robust and effective adaptive anticancer therapies. Herein, we present a proof-of-concept review for AgNPs-based proteogenomics and chemical metabolomics from various tumor cells with the help of several technologies, suggesting their promising use as drug carriers for cancer therapy. Full article
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