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Spotlight on Photoactivatable Liposomes beyond Drug Delivery: An Enabler of Multitargeting of Molecular Pathways
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    Spotlight on Photoactivatable Liposomes beyond Drug Delivery: An Enabler of Multitargeting of Molecular Pathways
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    • Mohammad A. Saad
      Mohammad A. Saad
      Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States
    • Tayyaba Hasan*
      Tayyaba Hasan
      Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, United States
      Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States
      *Email: [email protected]. Phone: 617-726-6996. FAX: 617-724-1345.
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    Bioconjugate Chemistry

    Cite this: Bioconjugate Chem. 2022, 33, 11, 2041–2064
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    https://doi.org/10.1021/acs.bioconjchem.2c00376
    Published October 5, 2022
    Copyright © 2022 American Chemical Society

    Abstract

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    The potential of photoactivating certain molecules, photosensitizers (PS), resulting in photochemical processes, has long been realized in the form of photodynamic therapy (PDT) for the management of several cancerous and noncancerous pathologies. With an improved understanding of the photoactivation process and its broader implications, efforts are being made to exploit the various facets of photoactivation, PDT, and the associated phenomenon of photodynamic priming in enhancing treatment outcomes, specifically in cancer therapeutics. The parallel emergence of nanomedicine, specifically liposome-based nanoformulations, and the convergence of the two fields of liposome-based drug delivery and PDT have led to the development of unique hybrid systems, which combine the exciting features of liposomes with adequate complementation through the photoactivation process. While initially liposomes carrying photosensitizers (PSs) were developed for enhancing the pharmacokinetics and the general applicability of PSs, more recently, PS-loaded liposomes, apart from their utility in PDT, have found several applications including enhanced targeting of drugs, coloading multiple therapeutic agents to enhance synergistic effects, imaging, priming, triggering drug release, and facilitating the escape of therapeutic agents from the endolysosomal complex. This review discusses the design strategies, potential, and unique attributes of these hybrid systems, with not only photoactivation as an attribute but also the ability to encapsulate multiple agents for imaging, biomodulation, priming, and therapy referred to as photoactivatable multiagent/inhibitor liposomes (PMILS) and their targeted versions─targeted PMILS (TPMILS). While liposomes have formed their own niche in nanotechnology and nanomedicine with several clinically approved formulations, we try to highlight how using PS-loaded liposomes could address some of the limitations and concerns usually associated with liposomes to overcome them and enhance their preclinical and clinical utility in the future.

    Copyright © 2022 American Chemical Society

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    This article is cited by 12 publications.

    1. Mohammad A. Saad, Stacey Grimaldo-Garcia, Allison Sweeney, Srivalleesha Mallidi, Tayyaba Hasan. Dual-Function Antibody Conjugate-Enabled Photoimmunotherapy Complements Fluorescence and Photoacoustic Imaging of Head and Neck Cancer Spheroids. Bioconjugate Chemistry 2024, 35 (1) , 51-63. https://doi.org/10.1021/acs.bioconjchem.3c00406
    2. Yulin Mo, Miffy H. Y. Cheng, Andrew D’Elia, Katie Doran, Lili Ding, Juan Chen, Pieter R. Cullis, Gang Zheng. Light-Activated siRNA Endosomal Release (LASER) by Porphyrin Lipid Nanoparticles. ACS Nano 2023, 17 (5) , 4688-4703. https://doi.org/10.1021/acsnano.2c10936
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    4. Derek Allen, Madeline JoAnna Szoo, Tessa D van Bergen, Ani Seppelin, Jeonghyun Oh, Mohammad A Saad. Near-infrared photoimmunotherapy: mechanisms, applications, and future perspectives in cancer research. Antibody Therapeutics 2025, 8 (1) , 68-85. https://doi.org/10.1093/abt/tbaf001
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    10. Gennaro Sanità, Maria Laura Alfieri, Barbara Carrese, Serena Damian, Brigida Silvestri, Vincenza Mele, Sebastiano Marra, Susan Mohammadi, Giuseppina Luciani, Annalisa Lamberti, Paola Manini. A Dihydroisoquinoline Platform Inspired from Natural Alkaloids as Ligand for Highly Cytotoxic Ruthenium-Based Photosensitizers: New Perspectives for Melanoma and Breast Cancer Treatment. 2024https://doi.org/10.2139/ssrn.4748998
    11. Taokun Luo, Yingjie Fan, Jianming Mao, Xiaomin Jiang, Luciana Albano, Eric Yuan, Tomas Germanas, Wenbin Lin. Metal‐Organic Layer Delivers 5‐Aminolevulinic Acid and Porphyrin for Dual‐Organelle‐Targeted Photodynamic Therapy. Angewandte Chemie 2023, 135 (22) https://doi.org/10.1002/ange.202301910
    12. Taokun Luo, Yingjie Fan, Jianming Mao, Xiaomin Jiang, Luciana Albano, Eric Yuan, Tomas Germanas, Wenbin Lin. Metal‐Organic Layer Delivers 5‐Aminolevulinic Acid and Porphyrin for Dual‐Organelle‐Targeted Photodynamic Therapy. Angewandte Chemie International Edition 2023, 62 (22) https://doi.org/10.1002/anie.202301910
    13. Van-An Duong, Thi-Thao-Linh Nguyen, Han-Joo Maeng. Recent Advances in Intranasal Liposomes for Drug, Gene, and Vaccine Delivery. Pharmaceutics 2023, 15 (1) , 207. https://doi.org/10.3390/pharmaceutics15010207

    Bioconjugate Chemistry

    Cite this: Bioconjugate Chem. 2022, 33, 11, 2041–2064
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.bioconjchem.2c00376
    Published October 5, 2022
    Copyright © 2022 American Chemical Society

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