Precision-engineered bacterial nanovectors for synergetic co-delivery to harness cellular senescence and immunomodulation for enhanced tumor eradication

IF 13.3 1区工程技术 Q1 ENGINEERING, CHEMICAL

Chemical Engineering Journal Pub Date : 2025-01-12 DOI:10.1016/j.cej.2025.159533

Zixuan Ye, Yuanzhuo Zhou, Lizhen Liang, Jiahui Zhao, Wenzheng Liu, Lingtong Meng, He Huang, Jingpeng Yang, Xinping Lin, Yanan Li

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引用次数: 0

Abstract

The combination of chemotherapy and immunotherapy, for example, doxorubicin and anti-PD-L1 antibody, has been a crucially synergistic cancer treatment. However, the poor intratumoral distribution and limited immunogenicity still impede its antitumor efficacy. To overcome these problems, live bacterial cell factory was introduced as delivery carrier to improve the effect, and further clarify the boosting mechanism of live bacteria in clinical of combination therapy. Herein, we rigorously optimized an anti-PD-L1 nb-expressed E. coli Nissle1917(ECNp) to exert accurate secretion in the hypoxia tumor environment, and doxorubicin-loaded liposome (Dox-Lip) was coated on the surface of EcNp by acid-sensitive imine bond linker. In malignant melanoma models, based on the superior antitumor effect, we found this EcNp-based carrier significantly triggers tumor cell senescence, which increases antigen presentation and causes IFN-γ-dependent immune response, reinforcing the immunogenic death induced by doxorubicin and upregulating the expression of PTEN in tumor cells to increase the sensitivity to anti-PD-L1 nb, playing a “hub” role of cascade-amplified antitumor effect. Moreover, with reliable safety, this EcNp-based hybrid provides a universal platform for the combined penetrant delivery of proteins and small-molecule drugs in advanced cancers.

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来源期刊

Chemical Engineering Journal 工程技术-工程：化工

CiteScore

21.70

自引率

9.30%

发文量

6781

审稿时长

2.4 months

期刊介绍： The Chemical Engineering Journal is an international research journal that invites contributions of original and novel fundamental research. It aims to provide an international platform for presenting original fundamental research, interpretative reviews, and discussions on new developments in chemical engineering. The journal welcomes papers that describe novel theory and its practical application, as well as those that demonstrate the transfer of techniques from other disciplines. It also welcomes reports on carefully conducted experimental work that is soundly interpreted. The main focus of the journal is on original and rigorous research results that have broad significance. The Catalysis section within the Chemical Engineering Journal focuses specifically on Experimental and Theoretical studies in the fields of heterogeneous catalysis, molecular catalysis, and biocatalysis. These studies have industrial impact on various sectors such as chemicals, energy, materials, foods, healthcare, and environmental protection.