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Development of Responsive Nanoparticles for Cancer Therapy
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Development of Responsive Nanoparticles for Cancer Therapy

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

Deadline for manuscript submissions: closed (25 July 2020) | Viewed by 58132

Special Issue Editor

Prof. Dr. Jordi Puiggalí

E-Mail Website
Guest Editor
Chemical Engineering Department, Universitat Politècnica de Catalunya, c/Eduard Maristany, 08019 Barcelona, Spain
Interests: structure of synthetic polymers; development of biodegradable polymers; study of nanocomposites; polymer physics; polymer crystallization
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cancer is the second leading cause of death worldwide with over 10 million cases each year. Surgery, radiotherapy, chemotherapy, and, to a lesser degree, immunotherapy and hyperthermia are typical treatments for malignant tumors. Nevertheless, the limitations of such therapies are evident. For example, conventional chemotherapeutic drugs have a short blood circulation time, very low specificity and a high risk of damaging healthy tissues.

Nanoscale polymeric systems have a great potential to fight against cancer and currently do not seem to have a sufficiently competitive alternative. Nanoparticles can preferentially leak into carcinogenic tissues taking advantage of the enhanced permeability and retention effect of malignant tumors. Nanosized systems can be designed with a great drug loading capacity, the ability to protect the payload from the immune system, a large surface to attach targeting ligands, stimuli responsiveness, and controlled release. Internal and external stimuli (e.g., pH, redox potential, enzyme expression, temperature, magnetic field, ultrasound, and light) can be used to target tumors and deliver the payload after administration. The potential of cancer nanomedicine is becoming enormous considering the versatility of polymer chemistry, which enables the development of complex architectures as well as simple hydrophilic nanogels.

This Special Issue of International Journal of Molecular Sciences will discuss, collect, and offer recent highlights and advances on the design of stimuli-responsive nanoparticles for cancer treatment.

Prof. Dr. Jordi Puiggalí
Guest Editor

Manuscript Submission Information

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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

  • nanogels
  • stimuli responsiveness
  • smart polymers
  • drug release
  • cancer therapy

Published Papers (16 papers)

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Editorial

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5 pages, 226 KiB  
Editorial
Development of Responsive Nanoparticles for Cancer Therapy
by Jordi Puiggalí
Int. J. Mol. Sci. 2023, 24(12), 10371; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms241210371 - 20 Jun 2023
Viewed by 832
Abstract
Great efforts are focused on the development of safe nano-carriers for the treatment of cancer in order to overcome some of the typical limitations of conventional therapies [...] Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)

Research

Jump to: Editorial, Review

26 pages, 4628 KiB  
Article
Characterization and Evaluation of Bone-Derived Nanoparticles as a Novel pH-Responsive Carrier for Delivery of Doxorubicin into Breast Cancer Cells
by Sheikh Tanzina Haque, Rowshan Ara Islam, Siew Hua Gan and Ezharul Hoque Chowdhury
Int. J. Mol. Sci. 2020, 21(18), 6721; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186721 - 14 Sep 2020
Cited by 10 | Viewed by 2712
Abstract
Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due [...] Read more.
Background: The limitations of conventional treatment modalities in cancer, especially in breast cancer, facilitated the necessity for developing a safer drug delivery system (DDS). Inorganic nano-carriers based on calcium phosphates such as hydroxyapatite (HA) and carbonate apatite (CA) have gained attention due to their biocompatibility, reduced toxicity, and improved therapeutic efficacy. Methods: In this study, the potential of goose bone ash (GBA), a natural derivative of HA or CA, was exploited as a pH-responsive carrier to successfully deliver doxorubicin (DOX), an anthracycline drug into breast cancer cells (e.g., MCF-7 and MDA-MB-231 cells). GBA in either pristine form or in suspension was characterized in terms of size, morphology, functional groups, cellular internalization, cytotoxicity, pH-responsive drug (DOX) release, and protein corona analysis. Results: The pH-responsive drug release study demonstrated the prompt release of DOX from GBA through its disintegration in acidic pH (5.5–6.5), which mimics the pH of the endosomal and lysosomal compartments as well as the stability of GBA in physiological pH (pH 7.5). The result of DOX binding with GBA indicated an increment in binding affinity with increasing concentrations of DOX. Cell viability and cytotoxicity analysis showed no innate toxicity of GBA particles. Both qualitative and quantitative cellular uptake analysis in both cell lines displayed an enhanced cellular internalization of DOX-loaded GBA compared to free DOX molecules. The protein corona spontaneously formed on the surface of GBA particles exhibited its affinity toward transport proteins, structural proteins, and a few other selective proteins. The adsorption of transport proteins could extend the circulation half-life in biological environment and increase the accumulation of the drug-loaded NPs through the enhanced permeability and retention (EPR) effect at the tumor site. Conclusion: These findings highlight the potential of GBA as a DDS to successfully deliver therapeutics into breast cancer cells. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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16 pages, 12250 KiB  
Article
Morphological Changes and Cellular Uptake of Functionalized Graphene Oxide Loaded with Protocatechuic Acid and Folic Acid in Hepatocellular Carcinoma Cancer Cell
by Kalaivani Buskaran, Mohd Zobir Hussein, Mohamad Aris Mohd Moklas and Sharida Fakurazi
Int. J. Mol. Sci. 2020, 21(16), 5874; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21165874 - 16 Aug 2020
Cited by 8 | Viewed by 2440
Abstract
The development of nanocomposites has swiftly changed the horizon of drug delivery systems in defining a new platform. Major understanding of the interaction of nanocomposites with cells and how the interaction influences intracellular uptake is an important aspect to study in order to [...] Read more.
The development of nanocomposites has swiftly changed the horizon of drug delivery systems in defining a new platform. Major understanding of the interaction of nanocomposites with cells and how the interaction influences intracellular uptake is an important aspect to study in order to ensure successful utilisation of the nanocomposites. Studies have suggested that the nanocomposites’ ability to permeate into biological cells is attributable to their well-defined physicochemical properties with nanoscale size, which is relevant to the nanoscale components of biology and cellular organelles. The functionalized graphene oxide coated with polyethylene glycol, loaded with protocatechuic acid and folic acid (GOP-PCA-FA) nanocomposite intracellular uptake was analysed using transmission electron microscope. The accumulation of fluorescent-labelled nanocomposites in the HepG2 cell was also analysed using a fluorescent microscope. In vitro cellular uptake showed that there was uptake of the drug from 24 h into the cells and the release study using fluorescently tagged nanocomposite demonstrated that release and accumulation were observed at 24 h and 48 h. Moreover, the migration ability of tumor cells is a key step in tumor progression which was observed 48 h after treatment. The GOP serves as a potential nanocarrier system which is capable of improving the therapeutic efficacy of drugs and biomolecules in medical as well as pharmaceutical applications through the enhanced intracellular release and accumulation of the encapsulated drugs. Nonetheless, it is essential to analyse the translocation of our newly developed GOP-PCA-FA, and its efficiency for drug delivery, effective cellular uptake, and abundant intracellular accumulation would be compromised by possible untoward side effects. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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23 pages, 6228 KiB  
Article
Optimization of the Preparation of Magnetic Liposomes for the Combined Use of Magnetic Hyperthermia and Photothermia in Dual Magneto-Photothermal Cancer Therapy
by Anilkumar T. S., Yu-Jen Lu and Jyh-Ping Chen
Int. J. Mol. Sci. 2020, 21(15), 5187; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155187 - 22 Jul 2020
Cited by 29 | Viewed by 3453
Abstract
In this work, we aimed to develop liposomal nanocomposites containing citric-acid-coated iron oxide magnetic nanoparticles (CMNPs) for dual magneto-photothermal cancer therapy induced by alternating magnetic field (AMF) and near-infrared (NIR) lasers. Toward this end, CMNPs were encapsulated in cationic liposomes to form nano-sized [...] Read more.
In this work, we aimed to develop liposomal nanocomposites containing citric-acid-coated iron oxide magnetic nanoparticles (CMNPs) for dual magneto-photothermal cancer therapy induced by alternating magnetic field (AMF) and near-infrared (NIR) lasers. Toward this end, CMNPs were encapsulated in cationic liposomes to form nano-sized magnetic liposomes (MLs) for simultaneous magnetic hyperthermia (MH) in the presence of AMF and photothermia (PT) induced by NIR laser exposure, which amplified the heating efficiency for dual-mode cancer cell killing and tumor therapy. Since the heating capability is directly related to the amount of entrapped CMNPs in MLs, while the liposome size is important to allow internalization by cancer cells, response surface methodology was utilized to optimize the preparation of MLs by simultaneously maximizing the encapsulation efficiency (EE) of CMNPs in MLs and minimizing the size of MLs. The experimental design was performed based on the central composite rotatable design. The accuracy of the model was verified from the validation experiments, providing a simple and effective method for fabricating the best MLs, with an EE of 87% and liposome size of 121 nm. The CMNPs and the optimized MLs were fully characterized from chemical and physical perspectives. In the presence of dual AMF and NIR laser treatment, a suspension of MLs demonstrated amplified heat generation from dual hyperthermia (MH)–photothermia (PT) in comparison with single MH or PT. In vitro cell culture experiments confirmed the efficient cellular uptake of the MLs from confocal laser scanning microscopy due to passive accumulation in human glioblastoma U87 cells originated from the cationic nature of MLs. The inducible thermal effects mediated by MLs after endocytosis also led to enhanced cytotoxicity and cumulative cell death of cancer cells in the presence of AMF–NIR lasers. This functional nanocomposite will be a potential candidate for bimodal MH–PT dual magneto-photothermal cancer therapy. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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17 pages, 8112 KiB  
Article
Green Synthesized Montmorillonite/Carrageenan/Fe3O4 Nanocomposites for pH-Responsive Release of Protocatechuic Acid and Its Anticancer Activity
by Yen Pin Yew, Kamyar Shameli, Shaza Eva Mohamad, Kar Xin Lee and Sin-Yeang Teow
Int. J. Mol. Sci. 2020, 21(14), 4851; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21144851 - 09 Jul 2020
Cited by 26 | Viewed by 2962
Abstract
Discovery of a novel anticancer drug delivery agent is important to replace conventional cancer therapies which are often accompanied by undesired side effects. This study demonstrated the synthesis of superparamagnetic magnetite nanocomposites (Fe3O4-NCs) using a green method. Montmorillonite (MMT) [...] Read more.
Discovery of a novel anticancer drug delivery agent is important to replace conventional cancer therapies which are often accompanied by undesired side effects. This study demonstrated the synthesis of superparamagnetic magnetite nanocomposites (Fe3O4-NCs) using a green method. Montmorillonite (MMT) was used as matrix support, while Fe3O4 nanoparticles (NPs) and carrageenan (CR) were used as filler and stabilizer, respectively. The combination of these materials resulted in a novel nanocomposite (MMT/CR/Fe3O4-NCs). A series of characterization experiments was conducted. The purity of MMT/CR/Fe3O4-NCs was confirmed by X-ray diffraction (XRD) analysis. High resolution transmission electron microscopy (HRTEM) analysis revealed the uniform and spherical shape of Fe3O4 NPs with an average particle size of 9.3 ± 1.2 nm. Vibrating sample magnetometer (VSM) analysis showed an Ms value of 2.16 emu/g with negligible coercivity which confirmed the superparamagnetic properties. Protocatechuic acid (PCA) was loaded onto the MMT/CR/Fe3O4-NCs and a drug release study showed that 15% and 92% of PCA was released at pH 7.4 and 4.8, respectively. Cytotoxicity assays showed that both MMT/CR/Fe3O4-NCs and MMT/CR/Fe3O4-PCA effectively killed HCT116 which is a colorectal cancer cell line. Dose-dependent inhibition was seen and the killing was enhanced two-fold by the PCA-loaded NCs (IC50–0.734 mg/mL) compared to the unloaded NCs (IC50–1.5 mg/mL). This study highlights the potential use of MMT/CR/Fe3O4-NCs as a biologically active pH-responsive drug delivery agent. Further investigations are warranted to delineate the mechanism of cell entry and cancer cell killing as well as to improve the therapeutic potential of MMT/CR/Fe3O4-NCs. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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15 pages, 5062 KiB  
Article
Effective Photodynamic Therapy for Colon Cancer Cells Using Chlorin e6 Coated Hyaluronic Acid-Based Carbon Nanotubes
by Prabhavathi Sundaram and Heidi Abrahamse
Int. J. Mol. Sci. 2020, 21(13), 4745; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21134745 - 03 Jul 2020
Cited by 58 | Viewed by 3243
Abstract
Colon cancer is the third major cancer contributor to mortality worldwide. Nanosized particles have attracted attention due to their possible contribution towards cancer treatment and diagnosis. Photodynamic therapy (PDT) is a cancer therapeutic modality that involves a light source, a photosensitizer and reactive [...] Read more.
Colon cancer is the third major cancer contributor to mortality worldwide. Nanosized particles have attracted attention due to their possible contribution towards cancer treatment and diagnosis. Photodynamic therapy (PDT) is a cancer therapeutic modality that involves a light source, a photosensitizer and reactive oxygen species. Carbon nanotubes are fascinating nanocarriers for drug delivery, cancer diagnosis and numerous potential applications due to their unique physicochemical properties. In this study, single walled carbon nanotubes (SWCNTs) were coupled with hyaluronic acid (HA) and chlorin e6 (Ce6) coated on the walls of SWCNTs. The newly synthesized nanobiocomposite was characterized using ultraviolet-visible spectroscopy, Fourier transform electron microscopy (FTIR), X-ray diffraction analysis (XRD), particle size analysis and zeta potential. The loading efficiency of the SWCNTs-HA for Ce6 was calculated. The toxicity of the nanobiocomposite was tested on colon cancer cells using PDT at a fluence of 5 J/cm2 and 10 J/cm2. After 24 h, cellular changes were observed via microscopy, LDH cytotoxicity assay and cell death induction using annexin propidium iodide. The results showed that the newly synthesized nanobiocomposite enhanced the ability of PDT to be a photosensitizer carrier and induced cell death in colon cancer cells. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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10 pages, 2099 KiB  
Communication
Photosensitive Supramolecular Micelle-Mediated Cellular Uptake of Anticancer Drugs Enhances the Efficiency of Chemotherapy
by Yihalem Abebe Alemayehu, Wen-Lu Fan, Fasih Bintang Ilhami, Chih-Wei Chiu, Duu-Jong Lee and Chih-Chia Cheng
Int. J. Mol. Sci. 2020, 21(13), 4677; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21134677 - 30 Jun 2020
Cited by 13 | Viewed by 2893
Abstract
The development of stimuli-responsive supramolecular micelles with high drug-loading contents that specifically induce significant levels of apoptosis in cancer cells remains challenging. Herein, we report photosensitive uracil-functionalized supramolecular micelles that spontaneously form via self-assembly in aqueous solution, exhibit sensitive photo-responsive behavior, and effectively [...] Read more.
The development of stimuli-responsive supramolecular micelles with high drug-loading contents that specifically induce significant levels of apoptosis in cancer cells remains challenging. Herein, we report photosensitive uracil-functionalized supramolecular micelles that spontaneously form via self-assembly in aqueous solution, exhibit sensitive photo-responsive behavior, and effectively encapsulate anticancer drugs at high drug-loading contents. Cellular uptake analysis and double-staining flow cytometric assays confirmed the presence of photo-dimerized uracil groups within the irradiated micelles remarkably enhanced endocytic uptake of the micelles by cancer cells and subsequently led to higher levels of apoptotic cell death, and thus improved the therapeutic effect in vitro. Thus, photo-dimerized uracil-functionalized supramolecular micelles may potentially represent an intelligent nanovehicle to improve the safety, efficacy, and applicability of cancer chemotherapy, and could also enable the development of nucleobase-based supramolecular micelles for multifunctional biomaterials and novel biomedical applications. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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Graphical abstract

18 pages, 3195 KiB  
Article
Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells
by Lamya H. Al-Wahaibi, Muneera S. M. Al-Saleem, Osama A. A. Ahmed, Usama A. Fahmy, Nabil A. Alhakamy, Basma G. Eid, Ashraf B. Abdel-Naim, Wael M. Abdel-Mageed, Maha M. AlRasheed and Gamal A. Shazly
Int. J. Mol. Sci. 2020, 21(11), 4138; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21114138 - 10 Jun 2020
Cited by 13 | Viewed by 2812
Abstract
Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) [...] Read more.
Accumulating evidence indicates that statins reduce the risk of different cancers and inhibit the proliferation of liver cancer cells. This study aims to explore whether the electrostatic conjugation of optimized fluvastatin (FLV) to human immunodeficiency virus type 1 (HIV-1) trans-activator transcription peptide (TAT) would enhance the anti-proliferative activity against HepG2 cells. FLV–TAT conjugation was optimized to achieve the lowest size with highest zeta potential. Nine formulae were constructed, using a factorial design with three factors—FLV concentration, TAT concentration, and pH of the medium—while the responses were zeta potential and size. The optimized formula showed a particle size of 199.24 nm and 29.14 mV zeta potential. Data indicates that conjugation of FLV to TAT (optimized formula) significantly enhances anti-proliferative activity and uptake by HepG2 cells when compared to raw FLV. Flow cytometry showed significant accumulation of cells in the pre-G phase, which highlights higher apoptotic activity. Annexin V staining indicated a significant increase in total cell death in early and late apoptosis. This was confirmed by significantly elevated caspase 3 in cells exposed to FLV–TAT preparation. In conclusion, the FLV–TAT optimized formula exhibited improved anti-proliferative action against HepG2. This is partially attributed to the enhanced apoptotic effects and cellular uptake of FLV. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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Graphical abstract

13 pages, 3095 KiB  
Article
Ruthenium Dendrimers against Human Lymphoblastic Leukemia 1301 Cells
by Sylwia Michlewska, Maksim Ionov, Aleksandra Szwed, Aneta Rogalska, Natalia Sanz del Olmo, Paula Ortega, Marta Denel, Damian Jacenik, Dzmitry Shcharbin, Francisco Javier de la Mata and Maria Bryszewska
Int. J. Mol. Sci. 2020, 21(11), 4119; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21114119 - 09 Jun 2020
Cited by 18 | Viewed by 2494
Abstract
Ruthenium atoms located in the surfaces of carbosilane dendrimers markedly increase their anti-tumor properties. Carbosilane dendrimers have been widely studied as carriers of drugs and genes owing to such characteristic features as monodispersity, stability, and multivalence. The presence of ruthenium in the dendrimer [...] Read more.
Ruthenium atoms located in the surfaces of carbosilane dendrimers markedly increase their anti-tumor properties. Carbosilane dendrimers have been widely studied as carriers of drugs and genes owing to such characteristic features as monodispersity, stability, and multivalence. The presence of ruthenium in the dendrimer structure enhances their successful use in anti-cancer therapy. In this paper, the activity of dendrimers of generation 1 and 2 against 1301 cells was evaluated using Transmission Electron Microscopy, comet assay and Real Time PCR techniques. Additionally, the level of reactive oxygen species (ROS) and changes of mitochondrial potential values were assessed. The results of the present study show that ruthenium dendrimers significantly decrease the viability of leukemia cells (1301) but show low toxicity to non-cancer cells (peripheral blood mononuclear cells—PBMCs). The in vitro test results indicate that the dendrimers injure the 1301 leukemia cells via the apoptosis pathway. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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23 pages, 4421 KiB  
Article
Effective Gold Nanoparticle-Antibody-Mediated Drug Delivery for Photodynamic Therapy of Lung Cancer Stem Cells
by Anine Crous and Heidi Abrahamse
Int. J. Mol. Sci. 2020, 21(11), 3742; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21113742 - 26 May 2020
Cited by 40 | Viewed by 4380
Abstract
Cancer stem cells (CSCs) are a leading contributor to lung cancer mortality rates. CSCs are responsible for tumor growth and recurrence through inhibition of drug-induced cell death, decreasing the effect of traditional cancer therapy and photodynamic therapy (PDT). PDT can be improved to [...] Read more.
Cancer stem cells (CSCs) are a leading contributor to lung cancer mortality rates. CSCs are responsible for tumor growth and recurrence through inhibition of drug-induced cell death, decreasing the effect of traditional cancer therapy and photodynamic therapy (PDT). PDT can be improved to successfully treat lung cancer by using gold nanoparticles (AuNPs), due to their size and shape, which have been shown to facilitate drug delivery and retention, along with the targeted antibody (Ab) mediated selection of CSCs. In this study, a nanobioconjugate (NBC) was constructed, using a photosensitizer (PS) (AlPcS4Cl), AuNPs and Abs. The NBC was characterized, using spectroscopy techniques. Photodynamic effects of the NBC on lung CSCs was evaluated, using biochemical assays 24 h post-irradiation, in order to establish its anticancer effect. Results showed successful conjugation of the nanocomposite. Localization of the NBC was seen to be in integral organelles involved in cell homeostasis. Biochemical responses of lung CSCs treated using AlPcS4Cl-AuNP and AlPcS4Cl-AuNP-Ab showed significant cell toxicity and cell death, compared to free AlPcS4Cl. The PDT effects were enhanced when using the NBC, showing significant lung CSC destruction to the point of eradication. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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29 pages, 14758 KiB  
Article
Cockle Shell-Derived Aragonite CaCO3 Nanoparticles for Co-Delivery of Doxorubicin and Thymoquinone Eliminates Cancer Stem Cells
by Kehinde Muibat Ibiyeye and Abu Bakar Zakaria Zuki
Int. J. Mol. Sci. 2020, 21(5), 1900; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051900 - 10 Mar 2020
Cited by 17 | Viewed by 3653
Abstract
Cancer stem cells CSCs (tumour-initiating cells) are responsible for cancer metastasis and recurrence associated with resistance to conventional chemotherapy. This study generated MBA MD231 3D cancer stem cells enriched spheroids in serum-free conditions and evaluated the influence of combined doxorubicin/thymoquinone-loaded cockle-shell-derived aragonite calcium [...] Read more.
Cancer stem cells CSCs (tumour-initiating cells) are responsible for cancer metastasis and recurrence associated with resistance to conventional chemotherapy. This study generated MBA MD231 3D cancer stem cells enriched spheroids in serum-free conditions and evaluated the influence of combined doxorubicin/thymoquinone-loaded cockle-shell-derived aragonite calcium carbonate nanoparticles. Single loaded drugs and free drugs were also evaluated. WST assay, sphere forming assay, ALDH activity analysis, Surface marker of CD44 and CD24 expression, apoptosis with Annexin V-PI kit, cell cycle analysis, morphological changes using a phase contrast light microscope, scanning electron microscopy, invasion assay and migration assay were carried out; The combination therapy showed enhanced apoptosis, reduction in ALDH activity and expression of CD44 and CD24 surface maker, reduction in cellular migration and invasion, inhibition of 3D sphere formation when compared to the free drugs and the single drug-loaded nanoparticle. Scanning electron microscopy showed poor spheroid formation, cell membrane blebbing, presence of cell shrinkage, distortion in the spheroid architecture; and the results from this study showed that combined drug-loaded cockle-shell-derived aragonite calcium carbonate nanoparticles can efficiently destroy the breast CSCs compared to single drug-loaded nanoparticle and a simple mixture of doxorubicin and thymoquinone. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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13 pages, 6005 KiB  
Article
Cell-Penetrating Peptide Modified PEG-PLA Micelles for Efficient PTX Delivery
by Qi Shuai, Yue Cai, Guangkuo Zhao and Xuanrong Sun
Int. J. Mol. Sci. 2020, 21(5), 1856; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21051856 - 09 Mar 2020
Cited by 20 | Viewed by 3770
Abstract
On account of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, amphiphilic block copolymer-based micelles have been widely utilized for chemotherapy drug delivery. In order to further improve the antitumor ability and to also reduce undesired side effects [...] Read more.
On account of their excellent capacity to significantly improve the bioavailability and solubility of chemotherapy drugs, amphiphilic block copolymer-based micelles have been widely utilized for chemotherapy drug delivery. In order to further improve the antitumor ability and to also reduce undesired side effects of drugs, cell-penetrating peptides have been used to functionalize the surface of polymer micelles endowed with the ability to target tumor tissues. Herein, we first synthesized functional polyethylene glycol-polylactic acid (PEG-PLA) tethered with maleimide at the PEG section of the block polymer, which was further conjugated with a specific peptide, the transactivating transcriptional activator (TAT), with an approved capacity of aiding translocation across the plasma membrane. Then, TAT-conjugated, paclitaxel-loaded nanoparticles were self-assembled into stable nanoparticles with a favorable size of 20 nm, and displayed a significantly increased cytotoxicity, due to their enhanced accumulation via peptide-mediated cellular association in human breast cancer cells (MCF-7) in vitro. But when further used in vivo, TAT-NP-PTX showed an acceleration of the drug’s plasma clearance rate compared with NP-PTX, and therefore weakened its antitumor activities in the mice model, because of its positive charge, its elimination by the endoplasmic reticulum system more quickly, and its targeting effect on normal cells leading towards being more toxic. So further modification of TAT-NP-PTX to shield TAT peptide’s positive charges may be a hot topic to overcome the present dilemma. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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16 pages, 2941 KiB  
Article
Enhanced Efficacy of PEGylated Liposomal Cisplatin: In Vitro and In Vivo Evaluation
by Mohsen Ghaferi, Mohammad Javad Asadollahzadeh, Azim Akbarzadeh, Hasan Ebrahimi Shahmabadi and Seyed Ebrahim Alavi
Int. J. Mol. Sci. 2020, 21(2), 559; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21020559 - 15 Jan 2020
Cited by 47 | Viewed by 3996
Abstract
This study aims to evaluate the potency of cisplatin (Cispt)-loaded liposome (LCispt) and PEGylated liposome (PLCispt) as therapeutic nanoformulations in the treatment of bladder cancer (BC). Cispt was loaded into liposomes using reverse-phase evaporation method, and the formulations were characterized using dynamic light [...] Read more.
This study aims to evaluate the potency of cisplatin (Cispt)-loaded liposome (LCispt) and PEGylated liposome (PLCispt) as therapeutic nanoformulations in the treatment of bladder cancer (BC). Cispt was loaded into liposomes using reverse-phase evaporation method, and the formulations were characterized using dynamic light scattering, scanning electron microscopy, dialysis membrane, and Fourier-transform infrared spectroscopy (FTIR) methods. The results showed that the particles were formed in spherical monodispersed shapes with a nanoscale size (221–274 nm) and controlled drug release profile. The cytotoxicity effects of LCispt and PLCispt were assessed in an in vitro environment, and the results demonstrated that PLCispt caused a 2.4- and 1.9-fold increase in the cytotoxicity effects of Cispt after 24 and 48 h, respectively. The therapeutic and toxicity effects of the formulations were also assessed on BC-bearing rats. The results showed that PLCispt caused a 4.8-fold increase in the drug efficacy (tumor volume of 11 ± 0.5 and 2.3 ± 0.1 mm3 in Cispt and PLCispt receiver rats, respectively) and a 3.3-fold decrease in the toxicity effects of the drug (bodyweight gains of 3% and 10% in Cispt and PLCispt receiver rats, respectively). The results of toxicity were also confirmed by histopathological studies. Overall, this study suggests that the PEGylation of LCispt is a promising approach to achieve a nanoformulation with enhanced anticancer effects and reduced toxicity compared to Cispt for the treatment of BC. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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17 pages, 10446 KiB  
Article
Incorporation of Chloramphenicol Loaded Hydroxyapatite Nanoparticles into Polylactide
by Manuel Rivas, Marc Pelechà, Lourdes Franco, Pau Turon, Carlos Alemán, Luis J. del Valle and Jordi Puiggalí
Int. J. Mol. Sci. 2019, 20(20), 5056; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20205056 - 11 Oct 2019
Cited by 12 | Viewed by 2845
Abstract
Chloramphenicol (CAM) has been encapsulated into hydroxyapatite nanoparticles displaying different morphologies and crystallinities. The process was based on typical precipitation of solutions containing phosphate and calcium ions and the addition of CAM once the hydroxyapatite nuclei were formed. This procedure favored a disposition [...] Read more.
Chloramphenicol (CAM) has been encapsulated into hydroxyapatite nanoparticles displaying different morphologies and crystallinities. The process was based on typical precipitation of solutions containing phosphate and calcium ions and the addition of CAM once the hydroxyapatite nuclei were formed. This procedure favored a disposition of the drug into the bulk parts of the nanoparticles and led to a fast release in aqueous media. Clear antibacterial activity was derived, being slightly higher for the amorphous samples due to their higher encapsulation efficiency. Polylactide (PLA) microfibers incorporating CAM encapsulated in hydroxyapatite nanoparticles were prepared by the electrospinning technique and under optimized conditions. Drug release experiments demonstrated that only a small percentage of the loaded CAM could be delivered to an aqueous PBS medium. This amount was enough to render an immediate bacteriostatic effect without causing a cytotoxic effect on osteoblast-like, fibroblasts, and epithelial cells. Therefore, the prepared scaffolds were able to retain CAM-loaded nanoparticles, being a reservoir that should allow a prolonged release depending on the polymer degradation rate. The studied system may have promising applications for the treatment of cancer since CAM has been proposed as a new antitumor drug. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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Review

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25 pages, 3156 KiB  
Review
Shape Anisotropic Iron Oxide-Based Magnetic Nanoparticles: Synthesis and Biomedical Applications
by Raquel G. D. Andrade, Sérgio R. S. Veloso and Elisabete M. S. Castanheira
Int. J. Mol. Sci. 2020, 21(7), 2455; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21072455 - 01 Apr 2020
Cited by 96 | Viewed by 8707
Abstract
Research on iron oxide-based magnetic nanoparticles and their clinical use has been, so far, mainly focused on the spherical shape. However, efforts have been made to develop synthetic routes that produce different anisotropic shapes not only in magnetite nanoparticles, but also in other [...] Read more.
Research on iron oxide-based magnetic nanoparticles and their clinical use has been, so far, mainly focused on the spherical shape. However, efforts have been made to develop synthetic routes that produce different anisotropic shapes not only in magnetite nanoparticles, but also in other ferrites, as their magnetic behavior and biological activity can be improved by controlling the shape. Ferrite nanoparticles show several properties that arise from finite-size and surface effects, like high magnetization and superparamagnetism, which make them interesting for use in nanomedicine. Herein, we show recent developments on the synthesis of anisotropic ferrite nanoparticles and the importance of shape-dependent properties for biomedical applications, such as magnetic drug delivery, magnetic hyperthermia and magnetic resonance imaging. A brief discussion on toxicity of iron oxide nanoparticles is also included. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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20 pages, 4458 KiB  
Review
Cancer Diagnosis through SERS and Other Related Techniques
by Maria Blanco-Formoso and Ramon A. Alvarez-Puebla
Int. J. Mol. Sci. 2020, 21(6), 2253; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21062253 - 24 Mar 2020
Cited by 53 | Viewed by 6161
Abstract
Cancer heterogeneity increasingly requires ultrasensitive techniques that allow early diagnosis for personalized treatment. In addition, they should preferably be non-invasive tools that do not damage surrounding tissues or contribute to body toxicity. In this context, liquid biopsy of biological samples such as urine, [...] Read more.
Cancer heterogeneity increasingly requires ultrasensitive techniques that allow early diagnosis for personalized treatment. In addition, they should preferably be non-invasive tools that do not damage surrounding tissues or contribute to body toxicity. In this context, liquid biopsy of biological samples such as urine, blood, or saliva represents an ideal approximation of what is happening in real time in the affected tissues. Plasmonic nanoparticles are emerging as an alternative or complement to current diagnostic techniques, being able to detect and quantify novel biomarkers such as specific peptides and proteins, microRNA, circulating tumor DNA and cells, and exosomes. Here, we review the latest ideas focusing on the use of plasmonic nanoparticles in coded and label-free surface-enhanced Raman scattering (SERS) spectroscopy. Moreover, surface plasmon resonance (SPR) spectroscopy, colorimetric assays, dynamic light scattering (DLS) spectroscopy, mass spectrometry or total internal reflection fluorescence (TIRF) microscopy among others are briefly examined in order to highlight the potential and versatility of plasmonics. Full article
(This article belongs to the Special Issue Development of Responsive Nanoparticles for Cancer Therapy)
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