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Brain Delivery of Biomimetic Phosphorus Dendrimer/Antibody Nanocomplexes for Enhanced Glioma Immunotherapy via Immune Modulation of T Cells and Natural Killer Cells.
Peng, Yamin; Zhan, Mengsi; Karpus, Andrii; Zou, Yu; Mignani, Serge; Majoral, Jean-Pierre; Shi, Xiangyang; Shen, Mingwu.
Affiliation
  • Peng Y; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, P. R. China.
  • Zhan M; College of Chemistry and Chemical Engineering, Donghua University, Shanghai 201620, P. R. China.
  • Karpus A; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai 201620, P. R. China.
  • Zou Y; Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, 31077 CEDEX 4 Toulouse, France.
  • Mignani S; Université Toulouse, 118 Route de Narbonne, 31077 CEDEX 4 Toulouse, France.
  • Majoral JP; Laboratoire de Chimie de Coordination du CNRS, 205 Route de Narbonne, 31077 CEDEX 4 Toulouse, France.
  • Shi X; Université Toulouse, 118 Route de Narbonne, 31077 CEDEX 4 Toulouse, France.
  • Shen M; CQM-Centro de Química da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal.
ACS Nano ; 18(14): 10142-10155, 2024 Apr 09.
Article in En | MEDLINE | ID: mdl-38526307
ABSTRACT
Fully mobilizing the activities of multiple immune cells is crucial to achieve the desired tumor immunotherapeutic efficacy yet still remains challenging. Herein, we report a nanomedicine formulation based on phosphorus dendrimer (termed AK128)/programmed cell death protein 1 antibody (aPD1) nanocomplexes (NCs) that are camouflaged with M1-type macrophage cell membranes (M1m) for enhanced immunotherapy of orthotopic glioma. The constructed AK128-aPD1@M1m NCs with a mean particle size of 160.3 nm possess good stability and cytocompatibility. By virtue of the decorated M1m having α4 and ß1 integrins, the NCs are able to penetrate the blood-brain barrier to codeliver both AK128 with intrinsic immunomodulatory activity and aPD1 to the orthotopic glioma with prolonged blood circulation time. We show that the phosphorus dendrimer AK128 can boost natural killer (NK) cell proliferation in peripheral blood mononuclear cells, while the delivered aPD1 enables immune checkpoint blockade (ICB) to restore the cytotoxic T cells and NK cells, thus promoting tumor cell apoptosis and simultaneously decreasing the tumor distribution of regulatory T cells vastly for improved glioma immunotherapy. The developed nanomedicine formulation with a simple composition achieves multiple modulations of immune cells by utilizing the immunomodulatory activity of nanocarrier and antibody-mediated ICB therapy, providing an effective strategy for cancer immunotherapy.
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Full text: 1 Database: MEDLINE Main subject: Dendrimers / Glioma Language: En Journal: ACS Nano Year: 2024 Type: Article

Full text: 1 Database: MEDLINE Main subject: Dendrimers / Glioma Language: En Journal: ACS Nano Year: 2024 Type: Article