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仿生磷树突/抗体纳米复合物经脑递送给增强的胶质瘤免疫治疗通过 T 细胞和自然杀伤细胞的免疫调节。

Brain Delivery of Biomimetic Phosphorus Dendrimer/Antibody Nanocomplexes for Enhanced Glioma Immunotherapy via Immune Modulation of T Cells and Natural Killer Cells.

机构信息

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.

College of Chemistry and Chemical Engineering, Donghua University, Shanghai 201620, P. R. China.

出版信息

ACS Nano. 2024 Apr 9;18(14):10142-10155. doi: 10.1021/acsnano.3c13088. Epub 2024 Mar 25.


DOI:10.1021/acsnano.3c13088
PMID: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 α and β 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.

摘要

充分调动多种免疫细胞的活性对于实现理想的肿瘤免疫治疗效果至关重要,但这仍然具有挑战性。在此,我们报告了一种基于磷树状大分子(命名为 AK128)/程序性死亡蛋白 1 抗体(aPD1)纳米复合物(NCs)的纳米药物制剂,该制剂被伪装成 M1 型巨噬细胞膜(M1m),用于增强原位脑胶质瘤的免疫治疗。构建的 AK128-aPD1@M1m NCs 的平均粒径为 160.3nm,具有良好的稳定性和细胞相容性。由于修饰的 M1m 具有 α 和 β 整合素,NCs 能够穿透血脑屏障,同时递送到原位脑胶质瘤中,具有延长的血液循环时间的 AK128 与内在免疫调节活性和 aPD1。我们表明,磷树状大分子 AK128 可以促进外周血单个核细胞中自然杀伤(NK)细胞的增殖,而递送到的 aPD1 能够进行免疫检查点阻断(ICB),以恢复细胞毒性 T 细胞和 NK 细胞,从而促进肿瘤细胞凋亡,同时大大减少肿瘤中调节性 T 细胞的分布,从而改善脑胶质瘤的免疫治疗。这种具有简单组成的纳米药物制剂通过利用纳米载体的免疫调节活性和抗体介导的 ICB 治疗,对免疫细胞进行了多种调节,为癌症免疫治疗提供了一种有效的策略。

相似文献

[1]
Brain Delivery of Biomimetic Phosphorus Dendrimer/Antibody Nanocomplexes for Enhanced Glioma Immunotherapy via Immune Modulation of T Cells and Natural Killer Cells.

ACS Nano. 2024-4-9

[2]
Phosphorous Dendron Micelles as a Nanomedicine Platform for Cooperative Tumor Chemoimmunotherapy via Synergistic Modulation of Immune Cells.

Adv Mater. 2023-1

[3]
Smart Nanomedicine to Enable Crossing Blood-Brain Barrier Delivery of Checkpoint Blockade Antibody for Immunotherapy of Glioma.

ACS Nano. 2022-1-25

[4]
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Adv Healthc Mater. 2024-11

[5]
Chemotherapy Mediated by Biomimetic Polymeric Nanoparticles Potentiates Enhanced Tumor Immunotherapy via Amplification of Endoplasmic Reticulum Stress and Mitochondrial Dysfunction.

Adv Mater. 2022-11

[6]
Dendrimer-Mediated Generation of a Metal-Phenolic Network for Antibody Delivery to Elicit Improved Tumor Chemo/Chemodynamic/Immune Therapy.

ACS Appl Mater Interfaces. 2025-1-22

[7]
Phosphorous dendrimer-mediated biomineralization for synergistic blockade therapy and hypoxia-activated chemotherapy of tumors.

Acta Biomater. 2025-6-1

[8]
Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells.

J Transl Med. 2008-12-18

[9]
Biomimetic Dendritic Cell-Based Nanovaccines for Reprogramming the Immune Microenvironment to Boost Tumor Immunotherapy.

ACS Nano. 2024-12-17

[10]
Regulatory activity of azabisphosphonate-capped dendrimers on human CD4+ T cell proliferation enhances ex-vivo expansion of NK cells from PBMCs for immunotherapy.

J Transl Med. 2009-9-24

引用本文的文献

[1]
Antibody-conjugated polymer nanoparticles for brain cancer.

Drug Deliv Transl Res. 2025-8-20

[2]
Prospects and applications of NK therapy in the treatment of gliomas (Review).

Oncol Rep. 2025-8

[3]
Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment.

Research (Wash D C). 2025-6-3

[4]
Construction of fibromodulin and borneol-clacked phosphorus dendrimer nanoparticles to reduce inflammation and oxidative stress in BBB to nursing care and ischemic stroke therapy.

Naunyn Schmiedebergs Arch Pharmacol. 2025-5-24

[5]
From induced pluripotent stem cell (iPSC) to universal immune cells: literature review of advances in a new generation of tumor therapies.

Transl Cancer Res. 2025-4-30

[6]
Nano drug delivery systems for advanced immune checkpoint blockade therapy.

Theranostics. 2025-4-13

[7]
Nanotherapeutics for Macrophage Network Modulation in Tumor Microenvironments: Targets and Tools.

Int J Nanomedicine. 2024-12-19

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