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      Hybrid Lymphatic Drug Delivery Vehicles as a New Avenue for Targeted Therapy: Lymphatic Trafficking, Applications, Challenges, and Future Horizons

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          Abstract

          Lymphatic drug targeting is an effective approach for targeting immunomodulators, and chemotherapeutic drugs at a specific organ or cellular location. The cellular, paracellular, and dendritic cell trafficking machinery are involved in the lymphatic transport of therapeutic agents. The engineering of triggered and hybrid lymphatic drug delivery systems (LDDS) is a promising strategy to fight cancer metastasis and microbial pandemics. Hybrid lymphatic drug delivery systems can be tailored and developed by grafting the conventional LDDS with biological agents. Thus, hybrid LDDS could collect the benefits of conventional and biological delivery systems. Moreover, the fabrication of triggered LDDS increases drug accumulation in the lymphatic system in the response to an internal stimulus such as pH, and redox status or external such as magnetic field, temperature, and light. Stimuli-responsive LDD systems prevent premature release of payload and mediate selective drug biodistribution. This improves therapeutic impact and reduces the systemic side effect of anticancer, immunomodulatory, and antimicrobial therapeutics. This review highlights the challenges and future horizons of nanoscaled-triggered LDDS and their influence on the lymphatic trafficking of therapeutic molecules.

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          Engineering precision nanoparticles for drug delivery

          Michael J. Mitchell, Margaret M. Billingsley, Rebecca M. Haley … (2020)
          In recent years, the development of nanoparticles has expanded into a broad range of clinical applications. Nanoparticles have been developed to overcome the limitations of free therapeutics and navigate biological barriers — systemic, microenvironmental and cellular — that are heterogeneous across patient populations and diseases. Overcoming this patient heterogeneity has also been accomplished through precision therapeutics, in which personalized interventions have enhanced therapeutic efficacy. However, nanoparticle development continues to focus on optimizing delivery platforms with a one-size-fits-all solution. As lipid-based, polymeric and inorganic nanoparticles are engineered in increasingly specified ways, they can begin to be optimized for drug delivery in a more personalized manner, entering the era of precision medicine. In this Review, we discuss advanced nanoparticle designs utilized in both non-personalized and precision applications that could be applied to improve precision therapies. We focus on advances in nanoparticle design that overcome heterogeneous barriers to delivery, arguing that intelligent nanoparticle design can improve efficacy in general delivery applications while enabling tailored designs for precision applications, thereby ultimately improving patient outcome overall.
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            Molecular principles of metastasis: a hallmark of cancer revisited

            Jawad Fares, Mohamad Y. Fares, Hussein H. Khachfe … (2020)
            Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths. Yet, it remains poorly understood. The continuous evolution of cancer biology research and the emergence of new paradigms in the study of metastasis have revealed some of the molecular underpinnings of this dissemination process. The invading tumor cell, on its way to the target site, interacts with other proteins and cells. Recognition of these interactions improved the understanding of some of the biological principles of the metastatic cell that govern its mobility and plasticity. Communication with the tumor microenvironment allows invading cancer cells to overcome stromal challenges, settle, and colonize. These characteristics of cancer cells are driven by genetic and epigenetic modifications within the tumor cell itself and its microenvironment. Establishing the biological mechanisms of the metastatic process is crucial in finding open therapeutic windows for successful interventions. In this review, the authors explore the recent advancements in the field of metastasis and highlight the latest insights that contribute to shaping this hallmark of cancer.
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              Cancer Cell Membrane-Coated Nanoparticles for Anticancer Vaccination and Drug Delivery

              Ronnie Fang, Che-Ming Hu, Brian T Luk … (2014)
              Cell-derived nanoparticles have been garnering increased attention due to their ability to mimic many of the natural properties displayed by their source cells. This top-down engineering approach can be applied toward the development of novel therapeutic strategies owing to the unique interactions enabled through the retention of complex antigenic information. Herein, we report on the biological functionalization of polymeric nanoparticles with a layer of membrane coating derived from cancer cells. The resulting core–shell nanostructures, which carry the full array of cancer cell membrane antigens, offer a robust platform with applicability toward multiple modes of anticancer therapy. We demonstrate that by coupling the particles with an immunological adjuvant, the resulting formulation can be used to promote a tumor-specific immune response for use in vaccine applications. Moreover, we show that by taking advantage of the inherent homotypic binding phenomenon frequently observed among tumor cells the membrane functionalization allows for a unique cancer targeting strategy that can be utilized for drug delivery applications.
              Article 0 comments Cited 471 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Gamaleldin I. Harisa: harisa@ksu.edu.sa
                Abdelrahman Y. Sherif: ashreef@ksu.edu.sa
                Fars K. Alanazi: afars@ksu.edu.sa
                Journal
                Journal ID (nlm-ta): J Membr Biol
                Journal ID (iso-abbrev): J Membr Biol
                Title: The Journal of Membrane Biology
                Publisher: Springer US (New York )
                ISSN (Print): 0022-2631
                ISSN (Electronic): 1432-1424
                Publication date (Electronic): 8 February 2023
                Pages: 1-24
                Affiliations
                [1 ]GRID grid.56302.32, ISNI 0000 0004 1773 5396, Kayyali Chair for Pharmaceutical Industry, College of Pharmacy, , King Saud University, ; Riyadh, Saudi Arabia
                [2 ]GRID grid.56302.32, ISNI 0000 0004 1773 5396, Department of Pharmaceutics, College of Pharmacy, , King Saud University, ; Riyadh, Saudi Arabia
                [3 ]GRID grid.411303.4, ISNI 0000 0001 2155 6022, Department of Biochemistry and Molecular Biology, College of Pharmacy, , Al-Azhar University, ; Nasr City, Cairo, Egypt
                Article
                Publisher ID: 280
                DOI: 10.1007/s00232-023-00280-2
                PMC ID: 9906606
                PubMed ID: 36752839
                SO-VID: bd131e86-c0bb-4e44-bf4b-a5a2fba32f1e
                Copyright © © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                Date received : 20 November 2022
                Date accepted : 28 January 2023
                Funding
                Funded by: Deanship of Scientific Research, King Saud University for funding through Vice Deanship of Scientific Research Chairs, Kayyali Chair for Pharmaceutical Industry, Department of Pharmaceutics, College of Pharmacy
                Award ID: AG-2022-6.
                Award Recipient :
                Categories
                Subject: Topical Review

                ScienceOpen disciplines: Molecular biology
                Keywords: lymphatic delivery,cancer metastasis,hybrid ldds,triggered ldd
                Data availability:
                ScienceOpen disciplines: Molecular biology
                Keywords: lymphatic delivery, cancer metastasis, hybrid ldds, triggered ldd

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