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牛血清白蛋白层状双氢氧化物原位致敏骨肉瘤：用CD40激动剂抗体增强抗肿瘤疗效

BSA-LDHs-cGAMP In Situ Sensitization of Osteosarcoma: Enhancing Antitumor Efficacy with CD40 Agonist Antibodies.

作者信息

Yan Feng, Jing Chengwei, Duan Shao, Xia Yifei, Xiao Runzhu, Shao Shuaiming, Xiao Zunyu, Chen Weiyu, Li Chao

机构信息

Department of Orthopedics, The People's Hospital of Suzhou New District, Suzhou 215000, China.

Department of Nuclear Medicine, The First Affiliated Hospital of Ningbo University, Ningbo 315100, China.

出版信息

ACS Biomater Sci Eng. 2025 Aug 11;11(8):4931-4940. doi: 10.1021/acsbiomaterials.5c00333. Epub 2025 Jul 13.

DOI:10.1021/acsbiomaterials.5c00333
PMID:40653701
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12344641/
Abstract

Osteosarcoma is a malignant bone tumor that is extremely aggressive and presents several therapeutic problems. Although CD40 agonist antibodies (αCD40) have demonstrated potential in improving T cell priming and reprogramming tumor-associated macrophages, osteosarcoma's poor immunogenicity leads to "cold" tumors that are challenging to cure. When it comes to triggering immunological responses, the STING pathway is essential. To further improve this impact, cGAMP was stabilized and delivered using layered double hydroxide (LDH) nanoparticles cross-linked with bovine serum albumin (BSA). BSA-LDHs-cGAMP improved the infiltration of CD40+ macrophages and DC cells, which, in turn, improved the therapeutic impact of αCD40 immunotherapy. These results offer a promising in situ cancer treatment and show the possibility of αCD40 boosters in bone tumor therapy.

摘要

骨肉瘤是一种极具侵袭性的恶性骨肿瘤，存在诸多治疗难题。尽管CD40激动剂抗体（αCD40）已显示出在改善T细胞启动和重编程肿瘤相关巨噬细胞方面的潜力，但骨肉瘤较差的免疫原性导致其成为难以治愈的“冷”肿瘤。在触发免疫反应方面，STING通路至关重要。为进一步增强这种效果，使用与牛血清白蛋白（BSA）交联的层状双氢氧化物（LDH）纳米颗粒来稳定和递送环状二核苷酸单磷酸腺苷（cGAMP）。BSA-LDHs-cGAMP改善了CD40+巨噬细胞和树突状细胞（DC细胞）的浸润，进而提高了αCD40免疫疗法的治疗效果。这些结果为原位癌症治疗提供了有前景的方案，并显示了αCD40增强剂在骨肿瘤治疗中的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/2a3c59166f5a/ab5c00333_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/707a028c4dae/ab5c00333_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/8c1620cd2213/ab5c00333_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/a531d32d676c/ab5c00333_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/adfd00536774/ab5c00333_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/2a3c59166f5a/ab5c00333_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/707a028c4dae/ab5c00333_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/8c1620cd2213/ab5c00333_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/a531d32d676c/ab5c00333_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/adfd00536774/ab5c00333_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bd0/12344641/2a3c59166f5a/ab5c00333_0005.jpg

相似文献

[1]
BSA-LDHs-cGAMP In Situ Sensitization of Osteosarcoma: Enhancing Antitumor Efficacy with CD40 Agonist Antibodies.

ACS Biomater Sci Eng. 2025-8-11

[2]
Osteosarcoma-targeting Pt prodrug amphiphile for enhanced chemo-immunotherapy via Ca trapping.

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[3]
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J Immunother Cancer. 2025-7-1

[4]
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Phytomedicine. 2025-6-9

[5]
The Anti-Metastatic Properties of Glutathione-Stabilized Gold Nanoparticles-A Preliminary Study on Canine Osteosarcoma Cell Lines.

Int J Mol Sci. 2025-6-25

[6]
Preparation and evaluation of Baicalin-loaded albumin nanoparticles for anti-breast cancer activity.

Int J Biol Macromol. 2025-7

[7]
Prescription of Controlled Substances: Benefits and Risks

2025-1

[8]
The safety and efficiency of photodynamic therapy for the treatment of osteosarcoma: A systematic review of in vitro experiment and animal model reports.

Photodiagnosis Photodyn Ther. 2022-12

[9]
Activation of HTR2B Suppresses Osteosarcoma Progression through the STAT1-NLRP3 Inflammasome Pathway and Promotes OASL1+ Macrophage Production to Enhance Antitumor Immunity.

Adv Sci (Weinh). 2025-8

[10]
Oncolytic reovirus enhances the effect of CEA immunotherapy when combined with PD1-PDL1 inhibitor in a colorectal cancer model.

Immunotherapy. 2025-4

本文引用的文献

[1]
Metal-based smart nanosystems in cancer immunotherapy.

Exploration (Beijing). 2024-3-22

[2]
Efficacy and safety of bispecific antibodies vs. immune checkpoint blockade combination therapy in cancer: a real-world comparison.

Mol Cancer. 2024-4-16

[3]
Recent progress of metal-based nanomaterials with anti-tumor biological effects for enhanced cancer therapy.

Exploration (Beijing). 2023-6-30

[4]
Advances in Osteosarcoma.

Curr Osteoporos Rep. 2023-8

[5]
The immune factors have complex causal regulation effects on bone mineral density.

Front Immunol. 2022

[6]
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STAR Protoc. 2022-9-16

[7]
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Trends Immunol. 2022-7

[8]
Bispecific antibodies increase the therapeutic window of CD40 agonists through selective dendritic cell targeting.

Nat Cancer. 2022-3

[9]
Pharmacodynamics and pharmacokinetics of PLGA-based doxorubicin-loaded implants for tumor therapy.

Drug Deliv. 2022-12

[10]
New Horizons in the Treatment of Osteosarcoma.

N Engl J Med. 2021-11-25

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