Local Exosome Inhibition Potentiates Mild Photothermal Immunotherapy Against Breast Cancer

Limited immune infiltration within the tumor microenvironment (TME) hampers the efficacy of immune checkpoint blockade (ICB) therapy. To enhance immune infiltration, mild photothermal therapy (PTT) is often combined with immunotherapy. However, the impact of mild PTT on the TME remains unclear. The bioinformatics analyses reveal that mild PTT amplifies immune cell infiltration and stimulates T-cell activity. Notably, it accelerates the release of tumor cell-derived exosomes (T<sub>EX</sub>) and upregulates PD-L1 expression on both tumor cells and T<sub>EX</sub>. Consequently, it is proposed that locally inhibiting T<sub>EX</sub> release is crucial for overcoming the adverse effects of mild PTT, thereby enhancing ICB therapy. Thus, a multi-stage drug delivery system is designed that concurrently delivers photosensitizers (reduced graphene oxide nanosheets, NRGO), anti-PD-L1 antibodies, and exosome inhibitors (sulfisoxazole). The system employs a temperature-sensitive lipid gel as the primary carrier, with NRGO serving as a secondary carrier that supports photothermal conversion and incorporation of sulfisoxazole. Importantly, controlled drug release is achieved using near-infrared radiation. The findings indicate that this local combination therapy remodels the immunosuppressive TME through exosome inhibition and enhanced immune cell infiltration, while also boosting T-cell activity to trigger systemic antitumor immunity, showcasing the remarkable efficacy of this combination strategy in eradicating cold tumors.

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Publication Details

Journal
Advanced Science
Published
2024-11-22
DOI
https://doi.org/10.1002/advs.202406328
Citations
23
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
5.38

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article

Local Exosome Inhibition Potentiates Mild Photothermal Immunotherapy Against Breast Cancer

Yifang Xiao, Mengjiao He, Fang Zhou, Yuan Ding et al.
23 citations
Advanced Science
Extracellular vesicles in disease
5.38
article

Local Exosome Inhibition Potentiates Mild Photothermal Immunotherapy Against Breast Cancer

Yifang Xiao, Mengjiao He, Fang Zhou, Yuan Ding, Yiyang Cao, Zhenyu Xu, Naicong Cai, Shengyi Wang, Qian Chen, Zhongyuan Wang, Jiasheng Tu, Guangji Wang, Jiameng Hu, Mengjuan Sun, Chunmeng Sun, Chunjiayu Li, Haiyang Hu, Yanan Li, Chen Wang
article en
23 citations

Abstract

Limited immune infiltration within the tumor microenvironment (TME) hampers the efficacy of immune checkpoint blockade (ICB) therapy. To enhance immune infiltration, mild photothermal therapy (PTT) is often combined with immunotherapy. However, the impact of mild PTT on the TME remains unclear. The bioinformatics analyses reveal that mild PTT amplifies immune cell infiltration and stimulates T-cell activity. Notably, it accelerates the release of tumor cell-derived exosomes (T<sub>EX</sub>) and upregulates PD-L1 expression on both tumor cells and T<sub>EX</sub>. Consequently, it is proposed that locally inhibiting T<sub>EX</sub> release is crucial for overcoming the adverse effects of mild PTT, thereby enhancing ICB therapy. Thus, a multi-stage drug delivery system is designed that concurrently delivers photosensitizers (reduced graphene oxide nanosheets, NRGO), anti-PD-L1 antibodies, and exosome inhibitors (sulfisoxazole). The system employs a temperature-sensitive lipid gel as the primary carrier, with NRGO serving as a secondary carrier that supports photothermal conversion and incorporation of sulfisoxazole. Importantly, controlled drug release is achieved using near-infrared radiation. The findings indicate that this local combination therapy remodels the immunosuppressive TME through exosome inhibition and enhanced immune cell infiltration, while also boosting T-cell activity to trigger systemic antitumor immunity, showcasing the remarkable efficacy of this combination strategy in eradicating cold tumors.

Advanced ScienceVol. 12(2)
Tongji University (CN), Nanjing Normal University (CN), China Pharmaceutical University (CN), Fudan University (CN), Shenzhen Bay Laboratory (CN), Shanghai Pulmonary Hospital (CN)
National Natural Science Foundation of China, China Pharmaceutical University, China Postdoctoral Science Foundation, Government of Jiangsu Province, Natural Science Foundation of Jiangsu Province, State Key Laboratory of Natural Medicines, Bijzonder Onderzoeksfonds UGent, Fundamental Research Funds for the Central Universities, Natural Science Foundation of Jiangsu Province for Distinguished Young Scholars
Good health and well-being
Openalex Percentile: Top 3%
Extracellular vesicles in disease
5.38
DOIOpen Access PDFOpenAlex
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