Citation: Xiaoyu Hou, Mingyang Liu, Hu Wu, Nan Wang, Xu Zhao, Xifeng Qin, Xiaomin Su, Hanwei Huang, Zihan Ma, Jiahao Liu, Onder Ergonul, Füsun Can, Wei Liu, Zhiqing Pang, Funan Liu. Differential releasing hydrogel loaded with oncolytic viruses and anti-CAFs drug to enhance oncology therapeutic efficacy[J]. Chinese Chemical Letters, ;2025, 36(5): 110106. doi: 10.1016/j.cclet.2024.110106 shu

Differential releasing hydrogel loaded with oncolytic viruses and anti-CAFs drug to enhance oncology therapeutic efficacy

Xiaoyu Hou ^{a, b, c, 1} ,
Mingyang Liu ^{a, b, c, 1} ,
Hu Wu ^{a, b, c, 1} ,
Nan Wang ^{a, c, 1} ,
Xu Zhao ^{a, b, c} ,
Xifeng Qin ^b ,
Xiaomin Su ^d ,
Hanwei Huang ^{a, b, c} ,
Zihan Ma ^{a, c} ,
Jiahao Liu ^{a, c} ,
Onder Ergonul ^e ,
Füsun Can ^e ,
Wei Liu ^{f, *,} ,
Zhiqing Pang ^{b, *,} ,
Funan Liu ^{a, c, g, *,}

a.
Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Shenyang 110001, China
b.
Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China
c.
Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors, China Medical University, Ministry of Education, Shenyang 110001, China
d.
Central Laboratory, First Affiliated Hospital, Institute (College) of Integrative Medicine, Dalian Medical University, Dalian 116021, China
e.
Koç University Iş Bank Center for Infectious Diseases (KUISCID), Koç University School of Medicine and American Hospital, Istanbul 34450, Turkey
f.
The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China
g.
Phase I Clinical Trials Center, The First Hospital, China Medical University, Shenyang 110102, China

39240031@qq.com

zqpang@fudan.edu.cn

fnliu@cmu.edu.cn

Received Date: 7 April 2024
Revised Date: 10 June 2024
Accepted Date: 11 June 2024
Available Online: 18 June 2024

Figures(5)

Interstitial hypertension and extracellular matrix (ECM) barriers imposed by cancer-associated fibroblasts (CAFs) at the tumor site significantly impede the retention of intratumorally administered oncolytic viruses (OVs) as well as their efficacy in infecting and eradicating tumor cells. Herein, a stable, controllable, and easily prepared hydrogel was developed for employing a differential release strategy to deliver OVs. The oncolytic herpes simplex virus-2 (oH2) particles were loaded within sodium alginate (ALG), together with the small molecule drug PT-100 targeting CAFs. The rapid release of PT-100 functions as an anti-CAFs agent, reducing ECM, and alleviating interstitial pressure at the tumor site. Consequently, the delayed release of oH2 could more effectively invade and eradicate tumor cells while also facilitating enhanced infiltration of immune cells into the tumor microenvironment, thereby establishing an immunologically favorable milieu against tumors. This approach holds significant potential for achieving highly efficient oncolytic virus therapy with minimal toxicity, particularly in tumors rich in stromal components.
- Cancer-associated fibroblasts,
- Oncolytic virus,
- Hydrogel,
- Differential release,
- Immunology
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