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Biomaterials

Biomaterials

IF: 12.8
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Gamabufotalin loaded micro-nanocomposites for multimodal therapy of metastatic TNBC by efficiently inducing ICD

Published:26 September 2024 DOI: PMID: 39366186
Jialong Fan , Yan Qin , Wensheng Qiu , Jiahao Liang , Chang Xiao , Qian Xie , Chunyi Tong , Liqin Yuan , Ying Long , Bin Liu

Abstract

Gamabufotalin (CS-6), a main active compound derived from Chinese medicine Chansu, exhibits a robust inhibitory effect on programmed death-ligand 1 (PD-L1) in triple-negative breast cancer (TNBC) cells. Despite its potential for tumor therapy, the medical application of CS-6 is constrained by its hydrophobic nature, lack of targeting capability, and weak immunogenic cell death (ICD) effect. To address these limitations and improve the therapeutic efficiency of this drug against metastatic TNBC, we designed a new kind of [email?protected] that integrates carboxy-Prussian blue nanoparticles (CPB NPs), CS-6, and attenuated Salmonella typhimurium (S.lux) for TNBC therapy. In vitro and in vivo results have confirmed that CS-6@CPB NPs were efficiently delivered to neoplastic tissue by the tumor hypoxic chemotaxis property of S.lux, wherein the nanomedicine induced significant tumor cell necroptosis and apoptosis via photothermal therapy (PTT) of CPB NPs and chemotherapy of CS-6, which elicited ICD and inhibited PD-L1 expression, resulting in dendritic cells (DCs) maturation and effector T cells activation to comprehensively eliminate tumors. Additionally, the [email?protected]?+?Laser treatment significantly transformed the immunosuppressive tumor microenvironment (TME), enhancing antitumor immunity through promoting the polarization of tumor-associated macrophages into antitumorigenic M1 and reducing Tregs recruitment. Consequently, this comprehensive therapy not only inhibited primary and abscopal tumor progression but also prevented TNBC metastasis, which significantly prolonged survival time in animal models. In summary, these findings indicated an alternative approach for metastatic TNBC therapy.

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Procduct Name CAS Molecular Formula Supplier Price
GAMABUFOTALIN 465-11-2 C24H34O5 157 suppliers Inquiry
GAMABUFOTALIN 465-11-2 C24H34O5 157 suppliers Inquiry
GAMABUFOTALIN 465-11-2 C24H34O5 157 suppliers Inquiry
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