Reactive oxygen species (ROS) play important roles in cell signaling pathways, while increased production of ROS may disrupt cellular homeostasis, giving rise to oxidative stress and a series of ...diseases. Utilizing these cell‐generated species as triggers for selective tuning polymer structures and properties represents a promising methodology for disease diagnosis and treatment. Recently, significant progress has been made in fabricating biomaterials including nanoparticles and macroscopic networks to interact with this dynamic physiological condition. These ROS‐responsive platforms have shown potential in a range of biomedical applications, such as cancer targeted drug delivery systems, cell therapy platforms for inflammation related disease, and so on.
Reactive Oxygen Species (ROS) responsive polymeric materials, including nanoparticles, scaffolds, and hydrogels, have received progressive attention for their potential in biomedical applications, such as drug delivery, tissue engineering, and antioxidation in vivo. ROS responsive moieties are capable of displaying unique variation under oxidative stress, such as hydrophobic‐hydrophilicity transition and ROS‐induced degradation. Representative polymeric materials containing ROS responsive units are summarized in this review.
Biodegradable polymers have been widely used and have greatly promoted the development of biomedical fields because of their biocompatibility and biodegradability. The development of biotechnology ...and medical technology has set higher requirements for biomedical materials. Novel biodegradable polymers with specific properties are in great demand. Biodegradable polymers can be classified as natural or synthetic polymers according to the source. Synthetic biodegradable polymers have found more versatile and diverse biomedical applications owing to their tailorable designs or modifications. This review presents a comprehensive introduction to various types of synthetic biodegradable polymers with reactive groups and bioactive groups, and further describes their structure, preparation procedures and properties. The focus is on advances in the past decade in functionalization and responsive strategies of biodegradable polymers and their biomedical applications. The possible future developments of the materials are also discussed.
Immunotherapy has become a powerful cancer treatment, but only a small fraction of patients have achieved durable benefits due to the immune escape mechanism. In this study, epigenetic regulation is ...combined with gene therapy-mediated immune checkpoint blockade to relieve this immune escape mechanism. PPD (i.e., mPEG-b-PLG/PEI-RT3/DNA) is developed to mediate plasmid-encoding shPD-L1 delivery by introducing multiple interactions (i.e., electrostatic, hydrogen bonding, and hydrophobic interactions) and polyproline II (PPII)-helix conformation, which downregulates PD-L1 expression on tumour cells to relieve the immunosuppression of T cells. Zebularine (abbreviated as Zeb), a DNA methyltransferase inhibitor (DNMTi), is used for the epigenetic regulation of the tumour immune microenvironment, thus inducing DC maturation and MHC I molecule expression to enhance antigen presentation. PPD plus Zeb combination therapy initiates a systemic anti-tumour immune response and effectively prevents tumour relapse and metastasis by generating durable immune memory. This strategy provides a scheme for tumour treatment and the inhibition of relapse and metastasis.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease associated with persistent multiarticular synovitis, cartilage destruction, and even loss of joint function. Although remarkable ...progress has been made in the clinical treatment of RA, long-term administration of anti-rheumatic drugs still suffers quite a few drawbacks, including high dose and high frequency of drug use, as well as dysfunction of the heart, liver, kidney, and so forth. For the above problems, nanotherapeutic agents are developed to avert non-specific binding and upregulate the efficacy by improving the accumulation of drugs in lesion tissues. In this article, some of the most frequently used anti-RA agents were summarized, and the recent treatment of RA with passive or active targeting nanotheranostics was systematically illustrated. In addition, the prospect of nanovehicles in clinical therapy of RA was discussed and predicted.
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Hypoxia‐activated prodrugs (HAPs) have the potential to selectively kill hypoxic cells and convert tumor hypoxia from a problem to a selective treatment advantage. However, HAPs are unsuccessful in ...most clinical trials owing to inadequate hypoxia within the treated tumors, as implied by a further substudy of a phase II clinical trial. Here, a novel strategy for the combination of HAPs plus vascular disrupting agent (VDA) nanomedicine for efficacious solid tumor therapy is developed. An effective VDA nanomedicine of poly(l‐glutamic acid)‐graft‐methoxy poly(ethylene glycol)/combretastatin A4 (CA4‐NPs) is prepared and can selectively enhance tumor hypoxia and boost a typical HAP tirapazamine (TPZ) therapy against metastatic 4T1 breast tumors. After treatment with the combination of TPZ plus CA4‐NPs, complete tumor reduction is observed in 4T1 xenograft mice (initial tumor volume is 180 mm3), and significant tumor shrinkage and antimetastatic effects are observed in challenging large tumors with initial volume of 500 mm3. The report here highlights the potential of using a combination of HAPs plus VDA nanomedicine in solid tumor therapy.
A novel strategy for the combination of hypoxia‐activated prodrug tirapazamine and vascular disrupting agent nanomedicine (CA4‐NPs) for efficacious solid tumor therapy is developed. After treatment, complete tumor reduction is observed in 4T1 xenograft mice (initial tumor volume is 180 mm3), and significant tumor shrinkage is observed in challenging large tumors with initial volume of 500 mm3.
Combination of photodynamic therapy (PDT) and photothermal therapy (PTT) generally requires different components to build a composite irradiated with different excitation lights. One component ...photoactive agent for enhanced combination of PDT and PTT under the excitation of a single wavelength light source is more urgent in tumor phototherapy via adjusting spatial arrangement of photoactive units. Herein, porphyrin-based covalent organic framework nanoparticles (COF-366 NPs) were synthesized to control the orderly spatial arrangement of the photoactive building units and firstly used for antitumor therapy in vivo. COF-366 NPs provide the simultaneous therapy of PDT and PTT under a single wavelength light source with the monitoring of photoacoustic (PA) imaging, which makes the operation simpler and more convenient. COF-366 NPs had achieved good phototherapy effect even in the face of large tumors. The prepared multifunctional COF-366 NPs open up a new avenue to phototherapeutic materials and expand the application range of covalent organic framework.
Gene therapy represents a promising cancer treatment featuring high efficacy and limited side effects, but it is stymied by a lack of safe and efficient gene-delivery vectors. Cationic polymers and ...lipid-based nonviral gene vectors have many advantages and have been extensively explored for cancer gene delivery, but their low gene-expression efficiencies relative to viral vectors limit their clinical translations. Great efforts have thus been devoted to developing new carrier materials and fabricating functional vectors aimed at improving gene expression, but the overall efficiencies are still more or less at the same level. This review analyzes the cancer gene-delivery cascade and the barriers, the needed nanoproperties and the current strategies for overcoming these barriers, and outlines PEGylation, surface-charge, size, and stability dilemmas in vector nanoproperties to efficiently accomplish the cancer gene-delivery cascade. Stability, surface, and size transitions (3S Transitions) are proposed to resolve those dilemmas and strategies to realize these transitions are comprehensively summarized. The review concludes with a discussion of the future research directions to design high-performance nonviral gene vectors.
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Controlled synthesis of polypeptides Liu, Yang; Li, Di; Ding, Jianxun ...
Chinese chemical letters,
12/2020, Letnik:
31, Številka:
12
Journal Article
Recenzirano
Polypeptides with various α-amino acids as structural units are promising biocompatible and biodegradable polymers as biomaterials. The precise chemical structures and low polydispersity indexes of ...polypeptides are critical factors for the potential biomedical applications, especially in the clinic. The controlled ring-opening polymerization of different α-amino acid N-carboxyanhydrides through the regulation of initiating systems, reaction conditions, and catalysts has been developed to synthesize the target polypeptides in the past few decades.
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Polypeptides are one kind of promising biodegradable and biocompatible biomedical polymers with the structural units of various α-amino acids. Polypeptides were first polymerized by the ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCAs) by Leuchs and Hermann in 1906. In the past decades, several effective strategies, including the selection of initiators, the adjustment of reaction conditions, and the introduction of catalysts, have been reported to improve the controllability of the ROP of various α-amino acid NCAs to synthesize different polypeptides with precise chemical structures and low polydispersity indexes. In this Review, the strategies, mechanisms, challenges, and opportunities for controlled synthesis of polypeptides by the ROP of different α-amino acid NCAs have been declared.
Skin wound repair is a multistage process involving multiple cellular and molecular interactions, which modulate the cell behaviors and dynamic remodeling of extracellular matrices to maximize ...regeneration and repair. Consequently, abnormalities in cell functions or pathways inevitably give rise to side effects, such as dysregulated inflammation, hyperplasia of nonmigratory epithelial cells, and lack of response to growth factors, which impedes angiogenesis and fibrosis. These issues may cause delayed wound healing or even non‐healing states. Current clinical therapeutic approaches are predominantly dedicated to preventing infections and alleviating topical symptoms rather than addressing the modulation of wound microenvironments to achieve targeted outcomes. Bioactive materials, relying on their chemical, physical, and biological properties or as carriers of bioactive substances, can affect wound microenvironments and promote wound healing at the molecular level. By addressing the mechanisms of wound healing from the perspective of cell behaviors, this review discusses how bioactive materials modulate the microenvironments and cell behaviors within the wounds during the stages of hemostasis, anti‐inflammation, tissue regeneration and deposition, and matrix remodeling. A deeper understanding of cell behaviors during wound healing is bound to promote the development of more targeted and efficient bioactive materials for clinical applications.
Bioactive materials with specific chemical, physical, and biological properties or as the carriers of bioactive cargoes, regulate wound microenvironments and promote wound healing effectively, which work through modulation of cell behaviors and dynamic remodeling of extracellular matrices during the stages of hemostasis, anti‐inflammation, tissue regeneration and deposition, and matrix remodeling, providing an emerging modality for clinical wound therapy.
Combining intracellularly active proteins with chemotherapeutics represents a promising strategy for synergistic cancer therapy. However, the lack of nanocarrier systems for delivery into cancer ...cells and controlled intracellular release of both physicochemically very distinct cargos significantly impedes the biomedical translation of this combination strategy in cancer therapy. Here, a well‐designed triblock copolymer, mPEG‐b‐PGCA‐b‐PGTA, is reported for application in a multistage cooperative drug delivery nanoplatform that accomplishes effective intracellular co‐delivery of hydrophilic ribonuclease A (RNase A) and hydrophobic doxorubicin (DOX). RNase A bioreversibly modified with phenylboronic acid groups via a ROS‐cleavable carbamate linker is incorporated into the triblock copolymer nanoparticles with high efficiency through a pH‐reversible phenylboronic acid–catechol linkage. The reversible covalent conjugations between RNase A and the triblock copolymer endow the nanoparticles with high stability under normal physiological conditions. Upon cellular internalization, the cooperative release of DOX and RNase A from the triblock copolymer nanoparticles is triggered at multiple stages by endosomal acidic environment and subsequent DOX‐enhanced intracellular ROS environment. This leads to enhanced synergistic anticancer effects as demonstrated both in vitro and in vivo. Given the versatility of dynamic covalent conjugations, this work provides a universal and stable platform for intracellular co‐delivery of various combinations of proteins and chemotherapeutics.
A multistage cooperative drug delivery nanoplatform is developed to concurrently load doxorubicin and phenylboronic‐acid‐modified RNase A through hydrophobic interactions and dynamic covalent conjugation, respectively. This nanoplatform efficiently delivers both cargos into tumor sites with high systemic stability and mediates low‐pH‐ and ROS‐triggered cooperative release of doxorubicin and RNase A within tumor cells, leading to enhanced combined anticancer efficacy.
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