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      Engineering bacterial outer membrane vesicles as transdermal nanoplatforms for photo-TRAIL–programmed therapy against melanoma

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          Abstract

          Transdermal photo-TRAIL therapy by transgenic E. coli–derived outer membrane vesicles eradicates melanoma completely.

          Abstract

          Melanoma is an aggressive cancer with rapid progression, relapse, and metastasis. Systemic therapies for melanoma exhibit limited anticancer potential and high toxicity. Here, we developed the outer membrane vesicles derived from transgenic Escherichia coli, modified with α vβ 3 integrin peptide targeting ligand and indocyanine green (named as I-P-OMVs), to induce the transdermal photo-TRAIL-programmed treatment in skin melanoma.-OMVs, which are outer membrane vesicles derived from transgenic Escherichia coli, modified with α vβ 3 integrin targeting ligand and indocyanine green (named as I-P-OMVs), to induce the transdermal photo-TRAIL–programmed treatment in skin melanoma. I-P-OMVs exhibited excellent stratum corneum penetration and specificity to melanoma. Upon near-infrared irritation, I-P-OMVs not only induced photothermal-photodynamic responses against primary melanoma spheroids but also activated TRAIL-induced apoptosis in disseminated tumor cells, resulting in a complete eradication of melanoma. I-P-OMVs are the first nanoplatforms to induce transdermal photo-TRAIL–programmed therapy in melanoma with enhanced antitumor performance and high safety, having great potential in cancer therapy.

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          Most cited references39

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          Transdermal drug delivery.

          Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, noncavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin's barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase its impact on medicine.
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            Every step of the way: integrins in cancer progression and metastasis

            Cell adhesion to the extracellular matrix is fundamental to tissue integrity and human health. Integrins are the main cellular adhesion receptors that through multifaceted roles as signalling molecules, mechanotransducers and key components of the cell migration machinery are implicated in nearly every step of cancer progression from primary tumour development to metastasis. Altered integrin expression is frequently detected in tumours, where integrins have roles in supporting oncogenic growth factor receptor (GFR) signalling and GFR-dependent cancer cell migration and invasion. In addition, integrins determine colonization of metastatic sites and facilitate anchorage-independent survival of circulating tumour cells. Investigations describing integrin engagement with a growing number of versatile cell surface molecules, including channels, receptors and secreted proteins, continue to lead to the identification of novel tumour-promoting pathways. Integrin-mediated sensing, stiffening and remodelling of the tumour stroma are key steps in cancer progression supporting invasion, acquisition of cancer stem cell characteristics and drug resistance. Given the complexity of integrins and their adaptable and sometimes antagonistic roles in cancer cells and the tumour microenvironment, therapeutic targeting of these receptors has been a challenge. However, novel approaches to target integrins and antagonism of specific integrin subunits in stringently stratified patient cohorts are emerging as potential ways forward.
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              Overcoming the challenges in administering biopharmaceuticals: formulation and delivery strategies.

              The formulation and delivery of biopharmaceutical drugs, such as monoclonal antibodies and recombinant proteins, poses substantial challenges owing to their large size and susceptibility to degradation. In this Review we highlight recent advances in formulation and delivery strategies--such as the use of microsphere-based controlled-release technologies, protein modification methods that make use of polyethylene glycol and other polymers, and genetic manipulation of biopharmaceutical drugs--and discuss their advantages and limitations. We also highlight current and emerging delivery routes that provide an alternative to injection, including transdermal, oral and pulmonary delivery routes. In addition, the potential of targeted and intracellular protein delivery is discussed.
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                Author and article information

                Journal
                Sci Adv
                Sci Adv
                SciAdv
                advances
                Science Advances
                American Association for the Advancement of Science
                2375-2548
                July 2020
                03 July 2020
                : 6
                : 27
                : eaba2735
                Affiliations
                [1 ]College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, PR China.
                [2 ]State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, PR China.
                [3 ]National Laboratory of Solid State Microstructures, Chemistry and Biomedicine Innovation Center, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210093, PR China.
                Author notes
                [*]

                These authors contributed equally to this work.

                []Corresponding author. Email: lhpeng@ 123456zju.edu.cn (L.-H.P.); gaojianqing@ 123456zju.edu.cn (J.-Q.G.); xning@ 123456nju.edu.cn (X.-H.N.)
                Author information
                http://orcid.org/0000-0001-9763-383X
                http://orcid.org/0000-0003-2267-5116
                http://orcid.org/0000-0003-3776-7355
                http://orcid.org/0000-0001-7093-4851
                http://orcid.org/0000-0002-3559-4043
                http://orcid.org/0000-0002-7956-2481
                http://orcid.org/0000-0003-1052-7060
                http://orcid.org/0000-0003-3453-9656
                Article
                aba2735
                10.1126/sciadv.aba2735
                7455490
                32923586
                e58e8ea1-329d-400a-aa10-73a723a40ac5
                Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

                This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 26 November 2019
                : 20 May 2020
                Categories
                Research Article
                Research Articles
                SciAdv r-articles
                Cancer
                Cancer
                Custom metadata
                Mariane Belen

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