Immunogenic hydrogel toolkit disturbing residual tumor "seeds" and pre-metastatic "soil" for inhibition of postoperative tumor recurrence and metastasis.
10.1016/j.apsb.2022.02.017
- Author:
Minglu ZHOU
1
;
Qingting ZUO
1
;
Yuan HUANG
1
;
Lian LI
1
Author Information
1. Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
- Publication Type:Journal Article
- Keywords:
CXCR4 inhibition;
Hydrogel;
Immunogenic cell death;
Immunotherapy;
Local therapy;
Postoperative treatment;
Pre-metastatic niche;
Tumor recurrence
- From:
Acta Pharmaceutica Sinica B
2022;12(8):3383-3397
- CountryChina
- Language:English
-
Abstract:
Tumor recurrence and metastasis is the leading cause of mortality for postoperative breast cancer patients. However, chemotherapy intervention after surgery is often unsatisfactory, because residual microtumors are difficult to target and require frequent administration. Here, an all-in-one and once-for-all drug depot based on in situ-formed hydrogel was applied to fit the irregular surgical trauma, and enable direct contact with residual tumors and sustained drug release. Our immunological analysis after resection of orthotopic breast tumor revealed that postsurgical activation of CXCR4-CXCL12 signal exacerbated the immunosuppression and correlated with adaptive upregulation of PD-L1 in recurrent tumors. Thus, a multifunctional hydrogel toolkit was developed integrating strategies of CXCR4 inhibition, immunogenicity activation and PD-L1 blockade. Our results showed that the hydrogel toolkit not only exerted local effect on inhibiting residual tumor cell "seeds" but also resulted in abscopal effect on disturbing pre-metastatic "soil". Furthermore, vaccine-like effect and durable antitumor memory were generated, which resisted a secondary tumor rechallenge in 100% cured mice. Strikingly, one single dose of such modality was able to eradicate recurrent tumors, completely prevent pulmonary metastasis and minimize off-target toxicity, thus providing an effective option for postoperative intervention.
