Citation: Lin Zhai, Yujie Shi, Yi Yan, An Lu, Xiaoyu Liu, Lei Lei, Yi Sun, Linxia Jiang, Xiangyu Wang, Honggang Qian, Jiancheng Wang. Local sustained release of PD-1 monoclonal antibody and lenvatinib by thermo-sensitive hydrogel for improving tumor immunotherapy[J]. Chinese Chemical Letters, ;2023, 34(8): 108104. doi: 10.1016/j.cclet.2022.108104 shu

Local sustained release of PD-1 monoclonal antibody and lenvatinib by thermo-sensitive hydrogel for improving tumor immunotherapy

Lin Zhai ^{a, 1} ,
Yujie Shi ^{a, b, 1} ,
Yi Yan ^a ,
An Lu ^a ,
Xiaoyu Liu ^a ,
Lei Lei ^a ,
Yi Sun ^a ,
Linxia Jiang ^a ,
Xiangyu Wang ^a ,
Honggang Qian ^{c, *,} ,
Jiancheng Wang ^{a, *,}

a.
Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
b.
Department of Pharmaceutical Analysis, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
c.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital & Institute, Beijing 100142, China

qianhg@sohu.com

wang-jc@bjmu.edu.cn

Received Date: 12 September 2022
Revised Date: 22 December 2022
Accepted Date: 25 December 2022
Available Online: 20 March 2023

Figures(5)

In clinic, the combination of intravenous pembrolizumab (PD-1 monoclonal antibody) with oral Lenvatinib (LEN) exhibited an enhanced synergistic benefit for cancer therapy. However, the clinical outcomes were always limited by the problems of inconsistent pharmacokinetic profiles of two drugs, lower drug accumulation in tumor and obvious side effects during the combination therapy. Here, in situ-forming thermosensitive hydrogels based on PLGA-PEG-PLGA triblock copolymers were prepared for local administration of anti-PD1 and LEN (P&L@Gel) to improve therapeutic efficacy and safety. After peritumoral or surgical resection site injection, the significant increased concentrations of both drugs in tumor were observed with the local sustained release of P&L@Gel. In comparison with the group of intraperitoneal anti-PD1 plus oral LEN (P-ip&L-po), significantly higher tumor inhibition efficiency on CT26 tumor models could be obtained in P&L@Gel group, even at the dose of one-eighth of the former, same tumor-inhibition effects could be achieved. The enhanced antitumor efficacy of P&L@Gel group was probably associated with the 2.2 folds of increased level of CD8+ T cells and the polarization of tumor associated macrophage from M2 to M1 along with the increased drug accumulation. Moreover, compared with the obvious side effects of P-ip&L-po group, no significant changes of PLT, ALT and UA in blood, as well as IL-1α and IL-1β in mice paws were observed between P&L@Gel group and untreated group. These results suggested that local administration of anti-PD1 and LEN with thermosensitive hydrogel could offer a potential strategy for tumors or tumor postoperative adjuvant treatment.
- Lenvatinib,
- PD-1 antibody,
- Thermosensitive hydrogels,
- Topical administration,
- Tumor immunotherapy
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沈阳化工大学材料科学与工程学院沈阳 110142