+1 Recommend
0 collections
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Drug-loaded microbubble delivery system to enhance PD-L1 blockade immunotherapy with remodeling immune microenvironment


      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.



          Although programmed cell death protein 1 (PD-1)/ programmed cell death-ligand protein 1 (PD-L1) checkpoint blockade immunotherapy demonstrates great promise in cancer treatment, poor infiltration of T cells resulted from tumor immunosuppressive microenvironment (TIME) and insufficient accumulation of anti-PD-L1 (αPD-L1) in tumor sites diminish the immune response. Herein, we reported a drug-loaded microbubble delivery system to overcome these obstacles and enhance PD-L1 blockade immunotherapy.


          Docetaxel (DTX) and imiquimod (R837)-loaded microbubbles (RD@MBs) were synthesized via a typical rotary evaporation method combined with mechanical oscillation. The targeted release of drugs was achieved by using the directional "bursting" capability of ultrasound-targeted microbubble destruction (UTMD) technology. The antitumor immune response by RD@MBs combining αPD-L1 were evaluated on 4T1 and CT26 tumor models.


          The dying tumor cells induced by DTX release tumor-associated antigens (TAAs), together with R837, promoted the activation, proliferation and recruitment of T cells. Besides, UTMD technology and DTX enhanced the accumulation of αPD-L1 in tumor sites. Moreover, RD@MBs remolded TIME, including the polarization of M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, and reduction of myeloid-derived suppressor cells (MDSCs). The RD@MBs + αPD-L1 synergistic therapy not only effectively inhibited the growth of primary tumors, but also significantly inhibited the mimic distant tumors as well as lung metastases.


          PD-L1 blockade immunotherapy was enhanced by RD@MBs delivery system.

          Supplementary Information

          The online version contains supplementary material available at 10.1186/s40824-023-00350-5.

          Related collections

          Most cited references52

          • Record: found
          • Abstract: found
          • Article: not found

          Cancer immunotherapy: harnessing the immune system to battle cancer.

          The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer immunotherapy. These successes also underscore the importance of understanding basic tumor immunology for successful clinical translation in treating patients with cancer. The Reviews in this Review Series focus on current developments in cancer immunotherapy, highlight recent advances in our understanding of basic aspects of tumor immunology, and suggest how these insights can lead to the development of new immunotherapeutic strategies.
            • Record: found
            • Abstract: found
            • Article: not found

            Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges

            Immunotherapy has emerged as a major therapeutic modality in oncology. Currently, however, the majority of patients with cancer do not derive benefit from these treatments. Vascular abnormalities are a hallmark of most solid tumours and facilitate immune evasion. These abnormalities stem from elevated levels of proangiogenic factors, such as VEGF and angiopoietin 2 (ANG2); judicious use of drugs targeting these molecules can improve therapeutic responsiveness, partially owing to normalization of the abnormal tumour vasculature that can, in turn, increase the infiltration of immune effector cells into tumours and convert the intrinsically immunosuppressive tumour microenvironment (TME) to an immunosupportive one. Immunotherapy relies on the accumulation and activity of immune effector cells within the TME, and immune responses and vascular normalization seem to be reciprocally regulated. Thus, combining antiangiogenic therapies and immunotherapies might increase the effectiveness of immunotherapy and diminish the risk of immune-related adverse effects. In this Perspective, we outline the roles of VEGF and ANG2 in tumour immune evasion and progression, and discuss the evidence indicating that antiangiogenic agents can normalize the TME. We also suggest ways that antiangiogenic agents can be combined with immune-checkpoint inhibitors to potentially improve patient outcomes, and highlight avenues of future research.
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Targeting photodynamic and photothermal therapy to the endoplasmic reticulum enhances immunogenic cancer cell death

              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.

                Author and article information

                Biomater Res
                Biomater Res
                Biomaterials Research
                BioMed Central (London )
                9 February 2023
                9 February 2023
                : 27
                [1 ]GRID grid.412461.4, ISNI 0000 0004 9334 6536, State Key Laboratory of Ultrasound in Medicine and Engineering, Institute of Ultrasound Imaging, , The Second Affiliated Hospital, Chongqing Medical University, ; Chongqing, 400010 People’s Republic of China
                [2 ]GRID grid.452206.7, ISNI 0000 0004 1758 417X, Ultrasound Department, , The First Affiliated Hospital of Chongqing Medical University, ; Chongqing, 400042 People’s Republic of China
                [3 ]GRID grid.203458.8, ISNI 0000 0000 8653 0555, Department of Pathology, College of Basic Medicine, , Chongqing Medical University, ; Chongqing, 400016 People’s Republic of China
                [4 ]GRID grid.203458.8, ISNI 0000 0000 8653 0555, Institute of Life Sciences, , Chongqing Medical University, ; Chongqing, 400016 People’s Republic of China
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                : 13 October 2022
                : 29 January 2023
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 82172092
                Award ID: 81871369
                Award ID: 82202175
                Award Recipient :
                Funded by: Key Project of Application Development Plan of Chongqing
                Award ID: cstc2019jscx-dxwtBX0004
                Award Recipient :
                Funded by: China Postdoctoral Science Foundation
                Award ID: 2021TQ0394
                Award ID: 2021M00637
                Award Recipient :
                Funded by: Chongqing Graduate Research Innovation Project
                Award ID: CYB22202
                Award Recipient :
                Funded by: Natural Science Foundation of Chongqing
                Award ID: CSTB2022NSCQ-MSX0093
                Award Recipient :
                Research Article
                Custom metadata
                © The Author(s) 2023

                ultrasound-targeted microbubble destruction (utmd),immune checkpoint blockade (icb),docetaxel (dtx),pd-l1,tumor immunosuppressive microenvironment


                Comment on this article