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8019 KiB

Open AccessArticle

Multi-Functional Nanogels for Tumor Targeting and Redox-Sensitive Drug and siRNA Delivery

by Giorgia Adamo, Natascia Grimaldi, Simona Campora, Donatella Bulone, Maria Luisa Bondì, Mohamad Al-Sheikhly, Maria Antonietta Sabatino, Clelia Dispenza and Giulio Ghersi

Molecules 2016, 21(11), 1594; https://doi.org/10.3390/molecules21111594 - 23 Nov 2016

Cited by 35 | Viewed by 8126

Abstract

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) [...] Read more.

(1) Background: A new family of nanosystems able to discern between normal and tumor cells and to release a therapeutic agent in controlled way were synthetized by e-beam irradiation. This technique permits to obtain biocompatible, sterile, carboxyl-functionalized polyvinylpyrrolidone (PVP-co-acrylic acid) nanogels (NGs); (2) Methods: Here, we performed a targeting strategy based on the recognition of over-expressed proteins on tumor cells, like the folate receptor. The selective targeting was demonstrated by co-culture studies and flow cytometry analysis, using folate conjugated NGs. Moreover, nanoparticles were conjugated to a chemotherapeutic drug or to a pro-apoptotic siRNA through a glutathione sensitive spacer, in order to obtain a controlled release mechanism, specific for cancer cells. The drug efficiency was tested on tumor and healthy cells by flow cytometric analysis, confocal and epifluorescence microscopy and cytotoxicity assay; the siRNA effect was investigated by RNAi experiment; (3) Results: The data obtained showed that the use of NGs permits a faster cargo release in cancer cells, in response to high cytosolic glutathione level, also improving their efficacy; (4) Conclusion: The possibility of releasing biological molecules in a controlled way and to recognize a specific tumor target allows overcoming the typical limits of the classic cancer therapy. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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3458 KiB

Open AccessArticle

Improvement of Peptide-Based Tumor Immunotherapy Using pH-Sensitive Fusogenic Polymer-Modified Liposomes

by Yuta Yoshizaki, Eiji Yuba, Toshihiro Komatsu, Keiko Udaka, Atsushi Harada and Kenji Kono

Molecules 2016, 21(10), 1284; https://doi.org/10.3390/molecules21101284 - 26 Sep 2016

Cited by 39 | Viewed by 7070

Abstract

To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) [...] Read more.

To establish peptide vaccine-based cancer immunotherapy, we investigated the improvement of antigenic peptides by encapsulation with pH-sensitive fusogenic polymer-modified liposomes for induction of antigen-specific immunity. The liposomes were prepared by modification of egg yolk phosphatidylcholine and l-dioleoyl phosphatidylethanolamine with 3-methyl-glutarylated hyperbranched poly(glycidol) (MGlu-HPG) and were loaded with antigenic peptides derived from ovalbumin (OVA) OVA-I (SIINFEKL), and OVA-II (PSISQAVHAAHAEINEAP_βA), which bind, respectively, to major histocompatibility complex (MHC) class I and class II molecules on dendritic cell (DCs). The peptide-loaded liposomes were taken up efficiently by DCs. The peptides were delivered into their cytosol. Administration of OVA-I-loaded MGlu-HPG-modified liposomes to mice bearing OVA-expressing E.G7-OVA tumors induced the activation of OVA-specific CTLs much more efficiently than the administration of free OVA-I peptide did. Mice strongly rejected E.G7-OVA cells after immunization with OVA-I peptide-loaded MGlu-HPG liposomes, although mice treated with free OVA-I peptide only slightly rejected the cells. Furthermore, efficient suppression of tumor volume was observed when tumor-bearing mice were immunized with OVA-I-peptide-loaded liposomes. Immunization with OVA-II-loaded MGlu-HPG-modified liposomes exhibited much lower tumor-suppressive effects. Results indicate that MGlu-HPG liposomes might be useful for improvement of CTL-inducing peptides for efficient cancer immunotherapy. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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9446 KiB

Open AccessArticle

Effects of Culture Substrate Made of Poly(N-isopropylacrylamide-co-acrylic acid) Microgels on Osteogenic Differentiation of Mesenchymal Stem Cells

by Zhuojun Dai, Yinglan Shu, Chao Wan and Chi Wu

Molecules 2016, 21(9), 1192; https://doi.org/10.3390/molecules21091192 - 9 Sep 2016

Cited by 14 | Viewed by 7046

Abstract

Poly(N-isopropylacrylamide) (PNIPAM)-based polymers and gels are widely known and studied for their thermoresponsive property. In the biomaterials category, they are regarded as a potential cell culture substrate, not only because of their biocompatibility, but also their special character of allowing controlled [...] Read more.

Poly(N-isopropylacrylamide) (PNIPAM)-based polymers and gels are widely known and studied for their thermoresponsive property. In the biomaterials category, they are regarded as a potential cell culture substrate, not only because of their biocompatibility, but also their special character of allowing controlled detachment of cells via temperature stimulus. Previous research about PNIPAM-based substrates mostly concentrated on their effects in cell adhesion and proliferation. In this study, however, we investigate the influence of the PNIPAM-based substrate on the differentiation capacity of stem cells. Especially, we choose P(NIPAM-AA) microgels as a culture dish coating and mesenchymal stem cells (MSCs) are cultured on top of the microgels. Interestingly, we find that the morphology of MSCs changes remarkably on a microgel-coated surface, from the original spindle form to a more stretched and elongated cell shape. Accompanied by the alternation in morphology, the expression of several osteogenesis-related genes is elevated even without inducing factors. In the presence of full osteogenic medium, MSCs on a microgel substrate show an enhancement in the expression level of osteopontin and alizarin red staining signals, indicating the physical property of substrate has a direct effect on MSCs differentiation. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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3051 KiB

Open AccessArticle

Gold Nanocluster Decorated Polypeptide/DNA Complexes for NIR Light and Redox Dual-Responsive Gene Transfection

by Qi Lei, Jing-Jing Hu, Lei Rong, Han Cheng, Yun-Xia Sun and Xian-Zheng Zhang

Molecules 2016, 21(8), 1103; https://doi.org/10.3390/molecules21081103 - 20 Aug 2016

Cited by 16 | Viewed by 7051

Abstract

Endo/lysosomal escape and subsequent nuclear translocation are recognized as the two major challenges for efficient gene transfection. Herein, nuclear localization signal (NLS) peptide sequences and oligomeric lysine sequences were crosslinked via disulfide bonds to obtain glutathione (GSH) reducible polypeptide (pNLS). The pNLS could [...] Read more.

Endo/lysosomal escape and subsequent nuclear translocation are recognized as the two major challenges for efficient gene transfection. Herein, nuclear localization signal (NLS) peptide sequences and oligomeric lysine sequences were crosslinked via disulfide bonds to obtain glutathione (GSH) reducible polypeptide (pNLS). The pNLS could condense DNA into compact positive-charged complexes with redox sensitivity, and then gold nanoclusters (AuNC) were further decorated to the surface via electrostatic interactions obtaining versatile pNLS/DNA/AuNC complexes. The AuNC could generate reactive oxygen species (ROS) under NIR-irradiation and accelerate the endo/lysosomal escape of the complexes, and then the pNLS sequence degraded by GSH in cytoplasm would release the DNA and facilitate the subsequent nuclear translocation for enhanced gene transfection. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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Review

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Open AccessReview

Recent Advances in Stimuli-Responsive Release Function Drug Delivery Systems for Tumor Treatment

by Chendi Ding, Ling Tong, Jing Feng and Jiajun Fu

Molecules 2016, 21(12), 1715; https://doi.org/10.3390/molecules21121715 - 20 Dec 2016

Cited by 121 | Viewed by 13299

Abstract

Benefiting from the development of nanotechnology, drug delivery systems (DDSs) with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can [...] Read more.

Benefiting from the development of nanotechnology, drug delivery systems (DDSs) with stimuli-responsive controlled release function show great potential in clinical anti-tumor applications. By using a DDS, the harsh side effects of traditional anti-cancer drug treatments and damage to normal tissues and organs can be avoided to the greatest extent. An ideal DDS must firstly meet bio-safety standards and secondarily the efficiency-related demands of a large drug payload and controlled release function. This review highlights recent research progress on DDSs with stimuli-responsive characteristics. The first section briefly reviews the nanoscale scaffolds of DDSs, including mesoporous nanoparticles, polymers, metal-organic frameworks (MOFs), quantum dots (QDs) and carbon nanotubes (CNTs). The second section presents the main types of stimuli-responsive mechanisms and classifies these into two categories: intrinsic (pH, redox state, biomolecules) and extrinsic (temperature, light irradiation, magnetic field and ultrasound) ones. Clinical applications of DDS, future challenges and perspectives are also mentioned. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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2148 KiB

Open AccessReview

A Review of Injectable Polymeric Hydrogel Systems for Application in Bone Tissue Engineering

by Pariksha J. Kondiah, Yahya E. Choonara, Pierre P. D. Kondiah, Thashree Marimuthu, Pradeep Kumar, Lisa C. Du Toit and Viness Pillay

Molecules 2016, 21(11), 1580; https://doi.org/10.3390/molecules21111580 - 21 Nov 2016

Cited by 173 | Viewed by 15071

Abstract

Biodegradable, stimuli-responsive polymers are essential platforms in the field of drug delivery and injectable biomaterials for application of bone tissue engineering. Various thermo-responsive hydrogels display water-based homogenous properties to encapsulate, manipulate and transfer its contents to the surrounding tissue, in the least invasive [...] Read more.

Biodegradable, stimuli-responsive polymers are essential platforms in the field of drug delivery and injectable biomaterials for application of bone tissue engineering. Various thermo-responsive hydrogels display water-based homogenous properties to encapsulate, manipulate and transfer its contents to the surrounding tissue, in the least invasive manner. The success of bioengineered injectable tissue modified delivery systems depends significantly on their chemical, physical and biological properties. Irrespective of shape and defect geometry, injectable therapy has an unparalleled advantage in which intricate therapy sites can be effortlessly targeted with minimally invasive procedures. Using material testing, it was found that properties of stimuli-responsive hydrogel systems enhance cellular responses and cell distribution at any site prior to the transitional phase leading to gelation. The substantially hydrated nature allows significant simulation of the extracellular matrix (ECM), due to its similar structural properties. Significant current research strategies have been identified and reported to date by various institutions, with particular attention to thermo-responsive hydrogel delivery systems, and their pertinent focus for bone tissue engineering. Research on future perspective studies which have been proposed for evaluation, have also been reported in this review, directing considerable attention to the modification of delivering natural and synthetic polymers, to improve their biocompatibility and mechanical properties. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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6261 KiB

Open AccessReview

Carbon-Based Materials for Photo-Triggered Theranostic Applications

by Karunya Albert and Hsin-Yun Hsu

Molecules 2016, 21(11), 1585; https://doi.org/10.3390/molecules21111585 - 20 Nov 2016

Cited by 57 | Viewed by 10402

Abstract

Carbon-based nanomaterials serve as a type of smart material for photo-triggered disease theranostics. The inherent physicochemical properties of these nanomaterials facilitate their use for less invasive treatments. This review summarizes the properties and applications of materials including fullerene, nanotubes, nanohorns, nanodots and nanographenes [...] Read more.

Carbon-based nanomaterials serve as a type of smart material for photo-triggered disease theranostics. The inherent physicochemical properties of these nanomaterials facilitate their use for less invasive treatments. This review summarizes the properties and applications of materials including fullerene, nanotubes, nanohorns, nanodots and nanographenes for photodynamic nanomedicine in cancer and antimicrobial therapies. Carbon nanomaterials themselves do not usually act as photodynamic therapy (PDT) agents owing to the high hydrophobicity, however, when the surface is passivated or functionalized, these materials become great vehicles for PDT. Moreover, conjugation of carbonaceous nanomaterials with the photosensitizer (PS) and relevant targeting ligands enhances properties such as selectivity, stability, and high quantum yield, making them readily available for versatile biomedical applications. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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1920 KiB

Open AccessReview

Stimuli-Responsive Polymeric Systems for Controlled Protein and Peptide Delivery: Future Implications for Ocular Delivery

by Pakama Mahlumba, Yahya E. Choonara, Pradeep Kumar, Lisa C. Du Toit and Viness Pillay

Molecules 2016, 21(8), 1002; https://doi.org/10.3390/molecules21081002 - 30 Jul 2016

Cited by 37 | Viewed by 8433

Abstract

Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of [...] Read more.

Therapeutic proteins and peptides have become notable in the drug delivery arena for their compatibility with the human body as well as their high potency. However, their biocompatibility and high potency does not negate the existence of challenges resulting from physicochemical properties of proteins and peptides, including large size, short half-life, capability to provoke immune responses and susceptibility to degradation. Various delivery routes and delivery systems have been utilized to improve bioavailability, patient acceptability and reduce biodegradation. The ocular route remains of great interest, particularly for responsive delivery of macromolecules due to the anatomy and physiology of the eye that makes it a sensitive and complex environment. Research in this field is slowly gaining attention as this could be the breakthrough in ocular drug delivery of macromolecules. This work reviews stimuli-responsive polymeric delivery systems, their use in the delivery of therapeutic proteins and peptides as well as examples of proteins and peptides used in the treatment of ocular disorders. Stimuli reviewed include pH, temperature, enzymes, light, ultrasound and magnetic field. In addition, it discusses the current progress in responsive ocular drug delivery. Furthermore, it explores future prospects in the use of stimuli-responsive polymers for ocular delivery of proteins and peptides. Stimuli-responsive polymers offer great potential in improving the delivery of ocular therapeutics, therefore there is a need to consider them in order to guarantee a local, sustained and ideal delivery of ocular proteins and peptides, evading tissue invasion and systemic side-effects. Full article

(This article belongs to the Special Issue Stimuli-Responsive Biomaterials in Biomedical Applications)

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