Citation: Xinyue Lan, Junguang Liang, Churan Wen, Xiaolong Quan, Huimin Lin, Qinqin Xu, Peixian Chen, Guangyu Yao, Dan Zhou, Meng Yu. Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy[J]. Chinese Chemical Letters, ;2024, 35(4): 108616. doi: 10.1016/j.cclet.2023.108616 shu

Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy

Xinyue Lan ^{a, b, 1} ,
Junguang Liang ^{a, 1} ,
Churan Wen ^b ,
Xiaolong Quan ^b ,
Huimin Lin ^b ,
Qinqin Xu ^b ,
Peixian Chen ^c ,
Guangyu Yao ^{a, *,} ,
Dan Zhou ^{c, *,} ,
Meng Yu ^{b, d, *,}

a.
Breast Center, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
b.
NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China
c.
Department of Breast Surgery, The First People's Hospital of Foshan, Foshan 528100, China
d.
Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China

yaogy@smu.edu.cn

zdan14@fsyyy.com

yumeng999@smu.edu.cn

Received Date: 16 April 2023
Revised Date: 23 May 2023
Accepted Date: 25 May 2023
Available Online: 26 May 2023

Figures(5)

Despite the synergy of immune checkpoint blockade (ICB) therapy and photodynamic therapy (PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strategies in "cold" tumors remains a great challenge. Here, we present a polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel loaded with photosensitizer chlorin e6 (Ce6) and programmed death-ligand 1 antibody (αPD-L1) for flexible local photoimmunotherapy with merely single-dosed administration. The presence of polyunsaturated fatty acid (docosahexaenoic acid, DHA) doped in particle membrane endows liposomes with flexibly reactive oxygen species (ROS)-responsive release capability, which was attributed to the presence of abundant unsaturated groups. The αPD-L1 was repeatedly induced to in situ release in response to the PDT under photo-exposure. The immunogenic cell death (ICD) effect of PDT evoked "cold" breast tumor to "hot" one, and then assisted the cascade released αPD-L1 to synergistically boost the immunotherapy. After a single dose of peritumoral administration of Lp(DHA)@CP Gel, the on-demand treatment can maximize patient compliance and safety by adjusting therapeutic behaviors via a photo on-off switch. This work presents a flexible medication platform, showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.
- Photodynamic therapy,
- Immunotherapy,
- Responsive release,
- Immunogenic cell death,
- Liposomal hydrogel
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