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      Dynamic responsiveness of self‐assembling peptide‐based nano‐drug systems

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          Abstract

          Dynamic‐responsive self‐assembly is the process of ordered supramolecular structure formation or reversible decomposition from building blocks. This process is driven by non‐covalent interactions based on complex stimulus‐responsive systems comprising different components within a microenvironment. Furthermore, stimuli‐responsive assembly‐disassembly is an intrinsic interaction process in organisms, indispensable in maintaining life activities and functions. However, the dynamic interactions between dynamically responsive nano‐drug systems (DRNSs) and biological systems remain unpredictable, which are a challenge for the precisely targeted therapy and controlled drug release of DRNSs in vivo. This review highlights novel self‐assembling peptide‐based nano‐drug systems and their biological interactions. By precisely controlling the shape and size of self‐assembled peptide nanomaterials, biologically simulated components with diverse biological functions and precise transport at the subcellular level can be achieved. We have also summarized the limitations and challenges of responsive self‐assembling peptide nanomaterials in clinical translation. Additionally, we have discussed the future perspectives of supramolecular therapeutics using signaling molecule gradient concentrations and efficiencies and highlighted the direction for developing clinically translatable smart nanomedicines.

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          Most cited references186

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          TGF-β attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells

          Therapeutic antibodies that block the programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer (mUC) 1–5 . However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here, we examined tumours from a large cohort of mUC patients treated with an anti–PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response was associated with CD8+ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden (TMB). Lack of response was associated with a signature of transforming growth factor β (TGF-β) signalling in fibroblasts, particularly in patients with CD8+ T cells that were excluded from the tumour parenchyma and instead found in the fibroblast- and collagen-rich peritumoural stroma—a common phenotype among patients with mUC. Using a mouse model that recapitulates this immune excluded phenotype, we found that therapeutic administration of a TGF-β blocking antibody together with anti–PD-L1 reduced TGF-β signalling in stromal cells, facilitated T cell penetration into the centre of the tumour, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding outcome in this setting and suggests that TGF-β shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T cell infiltration.
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            Nano based drug delivery systems: recent developments and future prospects

            Nanomedicine and nano delivery systems are a relatively new but rapidly developing science where materials in the nanoscale range are employed to serve as means of diagnostic tools or to deliver therapeutic agents to specific targeted sites in a controlled manner. Nanotechnology offers multiple benefits in treating chronic human diseases by site-specific, and target-oriented delivery of precise medicines. Recently, there are a number of outstanding applications of the nanomedicine (chemotherapeutic agents, biological agents, immunotherapeutic agents etc.) in the treatment of various diseases. The current review, presents an updated summary of recent advances in the field of nanomedicines and nano based drug delivery systems through comprehensive scrutiny of the discovery and application of nanomaterials in improving both the efficacy of novel and old drugs (e.g., natural products) and selective diagnosis through disease marker molecules. The opportunities and challenges of nanomedicines in drug delivery from synthetic/natural sources to their clinical applications are also discussed. In addition, we have included information regarding the trends and perspectives in nanomedicine area.
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              Principles of nanoparticle design for overcoming biological barriers to drug delivery.

              Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Obstacles, such as nonspecific distribution and inadequate accumulation of therapeutics, remain formidable challenges to drug developers. A reimagining of conventional nanoparticles is needed to successfully negotiate these impediments to drug delivery. Site-specific delivery of therapeutics will remain a distant reality unless nanocarrier design takes into account the majority, if not all, of the biological barriers that a particle encounters upon intravenous administration. By successively addressing each of these barriers, innovative design features can be rationally incorporated that will create a new generation of nanotherapeutics, realizing a paradigmatic shift in nanoparticle-based drug delivery.
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                Author and article information

                Contributors
                Journal
                Interdisciplinary Medicine
                Interdisciplinary Medicine
                Wiley
                2832-6245
                2832-6245
                January 2023
                January 04 2023
                January 2023
                : 1
                : 1
                Affiliations
                [1 ] Key Laboratory of Bioactive Materials Ministry of Education State Key Laboratory of Medicinal Chemical Biology College of Life Sciences Nankai University Tianjin China
                [2 ] Tianjin Key Laboratory of Inflammation Biology Department of Pharmacology School of Basic Medicine Tianjin Medical University Tianjin China
                [3 ] Department of Laboratory Medicine Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors Nanfang Hospital Southern Medical University Guangzhou China
                [4 ] Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical Sciences Southern Medical University Guangzhou China
                Article
                10.1002/INMD.20220005
                d5e9db6c-faf7-44ec-8075-11c305a86989
                © 2023

                http://creativecommons.org/licenses/by/4.0/

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