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      Advanced Strategies for Overcoming Endosomal/Lysosomal Barrier in Nanodrug Delivery

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          Abstract

          Nanocarriers have therapeutic potential to facilitate drug delivery, including biological agents, small-molecule drugs, and nucleic acids. However, their efficiency is limited by several factors; among which, endosomal/lysosomal degradation after endocytosis is the most important. This review summarizes advanced strategies for overcoming endosomal/lysosomal barriers to efficient nanodrug delivery based on the perspective of cellular uptake and intracellular transport mechanisms. These strategies include promoting endosomal/lysosomal escape, using non-endocytic methods of delivery to directly cross the cell membrane to evade endosomes/lysosomes and making a detour pathway to evade endosomes/lysosomes. On the basis of the findings of this review, we proposed several promising strategies for overcoming endosomal/lysosomal barriers through the smarter and more efficient design of nanodrug delivery systems for future clinical applications.

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          Routes and mechanisms of extracellular vesicle uptake

          Laura Mulcahy, Ryan Pink, David Carter (2014)
          Extracellular vesicles (EVs) are small vesicles released by donor cells that can be taken up by recipient cells. Despite their discovery decades ago, it has only recently become apparent that EVs play an important role in cell-to-cell communication. EVs can carry a range of nucleic acids and proteins which can have a significant impact on the phenotype of the recipient. For this phenotypic effect to occur, EVs need to fuse with target cell membranes, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest because they are deregulated in diseases such as cancer and they could be harnessed to deliver drugs to target cells. It is therefore important to understand the molecular mechanisms by which EVs are taken up into cells. This comprehensive review summarizes current knowledge of EV uptake mechanisms. Cells appear to take up EVs by a variety of endocytic pathways, including clathrin-dependent endocytosis, and clathrin-independent pathways such as caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft–mediated internalization. Indeed, it seems likely that a heterogeneous population of EVs may gain entry into a cell via more than one route. The uptake mechanism used by a given EV may depend on proteins and glycoproteins found on the surface of both the vesicle and the target cell. Further research is needed to understand the precise rules that underpin EV entry into cells.
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            Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials.

            Feng Zhao, Ying Zhao, Ying Liu … (2011)
            The interactions of nanoparticles with the soft surfaces of biological systems like cells play key roles in executing their biomedical functions and in toxicity. The discovery or design of new biomedical functions, or the prediction of the toxicological consequences of nanoparticles in vivo, first require knowledge of the interplay processes of the nanoparticles with the target cells. This article focusses on the cellular uptake, location and translocation, and any biological consequences, such as cytotoxicity, of the most widely studied and used nanoparticles, such as carbon-based nanoparticles, metallic nanoparticles, and quantum dots. The relevance of the size and shape, composition, charge, and surface chemistry of the nanoparticles in cells is considered. The intracellular uptake pathways of the nanoparticles and the cellular responses, with potential signaling pathways activated by nanoparticle interactions, are also discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
            Article 0 comments Cited 295 times – based on 0 reviews     Review now
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              Rational Design of Cancer Nanomedicine: Nanoproperty Integration and Synchronization.

              Nasha Qiu, Qihang Sun, Zhuxian Zhou … (2017)
              Current cancer nanomedicines can only mitigate adverse effects but fail to enhance therapeutic efficacies of anticancer drugs. Rational design of next-generation cancer nanomedicines should aim to enhance their therapeutic efficacies. Taking this into account, this review first analyzes the typical cancer-drug-delivery process of an intravenously administered nanomedicine and concludes that the delivery involves a five-step CAPIR cascade and that high efficiency at every step is critical to guarantee high overall therapeutic efficiency. Further analysis shows that the nanoproperties needed in each step for a nanomedicine to maximize its efficiency are different and even opposing in different steps, particularly what the authors call the PEG, surface-charge, size and stability dilemmas. To resolve those dilemmas in order to integrate all needed nanoproperties into one nanomedicine, stability, surface and size nanoproperty transitions (3S transitions for short) are proposed and the reported strategies to realize these transitions are comprehensively summarized. Examples of nanomedicines capable of the 3S transitions are discussed, as are future research directions to design high-performance cancer nanomedicines and their clinical translations.
              Article 0 comments Cited 285 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): Research (Wash D C)
                Journal ID (iso-abbrev): Research (Wash D C)
                Journal ID (publisher-id): RESEARCH
                Title: Research
                Publisher: AAAS
                ISSN (Electronic): 2639-5274
                Publication date (Electronic, pub): 24 May 2023
                Publication date (Electronic, collection): 2023
                Volume: 6
                Electronic Location Identifier: 0148
                Affiliations
                [ 1 ]Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences , Beijing 100700, China.
                [ 2 ]Department of Nephrology, and Shenzhen Clinical Research Centre for Geriatrics, Shenzhen People's Hospital, The First Affiliated Hospital, Southern University of Science and Technology , Shenzhen, Guangdong 518020, China.
                Author notes
                [*] [* ]Address correspondence to: cqiu@ 123456icmm.ac.cn (C.Q.); qyguo@ 123456icmm.ac.cn (Q.G.); jgwang@ 123456icmm.ac.cn (J.W.)
                [†]

                These authors contributed equally to this work.

                Article
                Publisher ID: 0148
                DOI: 10.34133/research.0148
                PMC ID: 10208951
                PubMed ID: 37250954
                SO-VID: 92b13a05-8a6a-4377-b91a-31e052a92265
                Copyright © Copyright © 2023 Chong Qiu et al.
                License:

                Exclusive licensee Science and Technology Review Publishing House. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License (CC BY 4.0).

                History
                Date received : 21 March 2023
                Date accepted : 27 April 2023
                Date: 24 May 2023
                Page count
                Figures: 8, Tables: 1, References: 204, Pages: 0
                Categories
                Subject: Review Article

                Data availability:

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