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      Recent progress of hypoxia-modulated multifunctional nanomedicines to enhance photodynamic therapy: opportunities, challenges, and future development

      review-article
      Author(s): a , a , b , b , c , a , a , ∗ , a , ∗
      Publication date (Electronic):
      Journal: Acta Pharmaceutica Sinica. B
      Publisher: Elsevier
      Keywords: Hypoxia, Photodynamic therapy, Cancer, Nanomedicine delivery systems, Oxygen, APCs, antigen-presenting cells, AQ4N, banoxantrone, Ce6, chlorin e6, CaO2, calcium dioxide, CeO2, cerium oxide, DC, dendritic cells, DOX, doxorubicin, DDS, drug delivery system, EPR, enhanced permeability and retention, FDA, U.S. Food and Drug Administration, HIF, hypoxia-inducible factor, HIF-1α, hypoxia-inducible factor-1α, H2O2, hydrogen peroxide, H2O, water, Hb, hemoglobin, HSA, human serum albumin, MDSC, myeloid derived suppressive cells, MDR1, multidrug resistance 1, MnO2, manganese dioxide, Mn-CDs, magnetofluorescent manganese-carbon dots, MB, methylene blue, NMR, nuclear magnetic resonance, O2.−, superoxide anion, OH., hydroxyl radical, 3O2, molecular oxygen, PDT, photodynamic therapy, PS, photosensitizers, PFC, perfluorocarbon, PFH, perfluoroethane, ROS, reactive oxygen species, RBCs, red blood cells, TAM, tumor-associated macrophages, TPZ, tirapazamine

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          Abstract

          Hypoxia, a salient feature of most solid tumors, confers invasiveness and resistance to the tumor cells. Oxygen-consumption photodynamic therapy (PDT) suffers from the undesirable impediment of local hypoxia in tumors. Moreover, PDT could further worsen hypoxia. Therefore, developing effective strategies for manipulating hypoxia and improving the effectiveness of PDT has been a focus on antitumor treatment. In this review, the mechanism and relationship of tumor hypoxia and PDT are discussed. Moreover, we highlight recent trends in the field of nanomedicines to modulate hypoxia for enhancing PDT, such as oxygen supply systems, down-regulation of oxygen consumption and hypoxia utilization. Finally, the opportunities and challenges are put forward to facilitate the development and clinical transformation of PDT.

          Graphical abstract

          Review of mechanisms and relationships of tumor hypoxia and photodynamic therapy as well as four nanomedicine delivery systems for manipulating tumor hypoxia to enhance the photodynamic therapy.

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          Controlled drug delivery vehicles for cancer treatment and their performance

          Sudipta Senapati, Arun Mahanta, Sunil Kumar … (2018)
          Although conventional chemotherapy has been successful to some extent, the main drawbacks of chemotherapy are its poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, development of multiple drug resistance, and non-specific targeting. The main aim in the development of drug delivery vehicles is to successfully address these delivery-related problems and carry drugs to the desired sites of therapeutic action while reducing adverse side effects. In this review, we will discuss the different types of materials used as delivery vehicles for chemotherapeutic agents and their structural characteristics that improve the therapeutic efficacy of their drugs and will describe recent scientific advances in the area of chemotherapy, emphasizing challenges in cancer treatments.
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            Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death

            Wei Li, Jie Yang, Lihua Luo … (2019)
            Immunogenic cell death (ICD)-associated immunogenicity can be evoked through reactive oxygen species (ROS) produced via endoplasmic reticulum (ER) stress. In this study, we generate a double ER-targeting strategy to realize photodynamic therapy (PDT) photothermal therapy (PTT) immunotherapy. This nanosystem consists of ER-targeting pardaxin (FAL) peptides modified-, indocyanine green (ICG) conjugated- hollow gold nanospheres (FAL-ICG-HAuNS), together with an oxygen-delivering hemoglobin (Hb) liposome (FAL-Hb lipo), designed to reverse hypoxia. Compared with non-targeting nanosystems, the ER-targeting naosystem induces robust ER stress and calreticulin (CRT) exposure on the cell surface under near-infrared (NIR) light irradiation. CRT, a marker for ICD, acts as an ‘eat me’ signal to stimulate the antigen presenting function of dendritic cells. As a result, a series of immunological responses are activated, including CD8+ T cell proliferation and cytotoxic cytokine secretion. In conclusion, ER-targeting PDT-PTT promoted ICD-associated immunotherapy through direct ROS-based ER stress and exhibited enhanced anti-tumour efficacy.
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              Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy

              Yuhao Cheng, Hao Cheng, Chenxiao Jiang … (2015)
              Photodynamic therapy (PDT) kills cancer cells by converting tumour oxygen into reactive singlet oxygen (1O2) using a photosensitizer. However, pre-existing hypoxia in tumours and oxygen consumption during PDT can result in an inadequate oxygen supply, which in turn hampers photodynamic efficacy. Here to overcome this problem, we create oxygen self-enriching photodynamic therapy (Oxy-PDT) by loading a photosensitizer into perfluorocarbon nanodroplets. Because of the higher oxygen capacity and longer 1O2 lifetime of perfluorocarbon, the photodynamic effect of the loaded photosensitizer is significantly enhanced, as demonstrated by the accelerated generation of 1O2 and elevated cytotoxicity. Following direct injection into tumours, in vivo studies reveal tumour growth inhibition in the Oxy-PDT-treated mice. In addition, a single-dose intravenous injection of Oxy-PDT into tumour-bearing mice significantly inhibits tumour growth, whereas traditional PDT has no effect. Oxy-PDT may enable the enhancement of existing clinical PDT and future PDT design.
              Article 0 comments Cited 312 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Qikun Jiang
                Zhonggui He
                Journal
                Journal ID (nlm-ta): Acta Pharm Sin B
                Journal ID (iso-abbrev): Acta Pharm Sin B
                Title: Acta Pharmaceutica Sinica. B
                Publisher: Elsevier
                ISSN (Print): 2211-3835
                ISSN (Electronic): 2211-3843
                Publication date PMC-release: 13 January 2020
                Publication date (Print): August 2020
                Publication date (Electronic): 13 January 2020
                Volume: 10
                Issue: 8
                Pages: 1382-1396
                Affiliations
                [a ]Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang 110016, China
                [b ]School of Pharmacy, Guangxi University of Chinese Medicine, Nanning 530200, China
                [c ]Department of Pharmaceutics, the Second Hospital of Dalian Medical University, Dalian 116023, China
                Author notes
                [∗ ]Corresponding authors. Tel./Fax: +86 24 23986325. jiangqikunlqq@ 123456163.com hezhgui_student@ 123456aliyun.com
                Article
                Publisher ID: S2211-3835(19)31373-5
                DOI: 10.1016/j.apsb.2020.01.004
                PMC ID: 7488364
                PubMed ID: 32963938
                SO-VID: 2806a4b2-aec0-4fba-b949-a582e9cd782b
                Copyright © © 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 28 September 2019
                Date revision received : 12 November 2019
                Date accepted : 27 November 2019
                Categories
                Subject: Review

                Keywords: hypoxia,photodynamic therapy,cancer,nanomedicine delivery systems,oxygen,apcs, antigen-presenting cells,aq4n, banoxantrone,ce6, chlorin e6,cao2, calcium dioxide,ceo2, cerium oxide,dc, dendritic cells,dox, doxorubicin,dds, drug delivery system,epr, enhanced permeability and retention,fda, u.s. food and drug administration,hif, hypoxia-inducible factor,hif-1α, hypoxia-inducible factor-1α,h2o2, hydrogen peroxide,h2o, water,hb, hemoglobin,hsa, human serum albumin,mdsc, myeloid derived suppressive cells,mdr1, multidrug resistance 1,mno2, manganese dioxide,mn-cds, magnetofluorescent manganese-carbon dots,mb, methylene blue,nmr, nuclear magnetic resonance,o2.−, superoxide anion,oh., hydroxyl radical,3o2, molecular oxygen,pdt, photodynamic therapy,ps, photosensitizers,pfc, perfluorocarbon,pfh, perfluoroethane,ros, reactive oxygen species,rbcs, red blood cells,tam, tumor-associated macrophages,tpz, tirapazamine
                Data availability:
                Keywords: hypoxia, photodynamic therapy, cancer, nanomedicine delivery systems, oxygen, apcs, antigen-presenting cells, aq4n, banoxantrone, ce6, chlorin e6, cao2, calcium dioxide, ceo2, cerium oxide, dc, dendritic cells, dox, doxorubicin, dds, drug delivery system, epr, enhanced permeability and retention, fda, u.s. food and drug administration, hif, hypoxia-inducible factor, hif-1α, hypoxia-inducible factor-1α, h2o2, hydrogen peroxide, h2o, water, hb, hemoglobin, hsa, human serum albumin, mdsc, myeloid derived suppressive cells, mdr1, multidrug resistance 1, mno2, manganese dioxide, mn-cds, magnetofluorescent manganese-carbon dots, mb, methylene blue, nmr, nuclear magnetic resonance, o2.−, superoxide anion, oh., hydroxyl radical, 3o2, molecular oxygen, pdt, photodynamic therapy, ps, photosensitizers, pfc, perfluorocarbon, pfh, perfluoroethane, ros, reactive oxygen species, rbcs, red blood cells, tam, tumor-associated macrophages, tpz, tirapazamine

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