A bio-responsive, cargo-catchable gel for postsurgical tumor treatment via ICD-based immunotherapy

被引:26
作者
Chen, Qian [1 ,2 ]
Zhou, Shuai [1 ,2 ]
Ding, Yuan [1 ,2 ,4 ,5 ,6 ]
Chen, Dali [1 ,2 ]
Dahiru, Naseer Sintali [1 ,2 ]
Tang, Hailei [1 ,2 ]
Xu, Hui [1 ,2 ]
Ji, Meng [1 ,2 ]
Wang, Xueyi [1 ,2 ]
Li, Zixuan [1 ,2 ]
Chen, Qinying [1 ,2 ]
Li, Yanan [1 ,2 ,3 ]
Tu, Jiasheng [1 ,2 ]
Sun, Chunmeng [1 ,2 ]
机构
[1] China Pharmaceut Univ, Sch Pharm, State Key Lab Nat Med, NMPA Key Lab Res & Evaluat Pharmaceut Preparat &, 24 Tong Jia Xiang, Nanjing 210009, Peoples R China
[2] China Pharmaceut Univ, Sch Pharm, Dept Pharmaceut, 24 Tong Jia Xiang, Nanjing 210009, Peoples R China
[3] Nanjing Normal Univ, Sch Food Sci & Pharmaceut Engn, Nanjing 201203, Peoples R China
[4] Minist Educ, Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China
[5] Fudan Univ, Sch Pharm, Dept Pharmaceut, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China
[6] Fudan Univ, Collaborat Innovat Ctr Brain Sci, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
Postsurgical; Gel depot; Combination immunotherapy; Immunogenic cell death (ICD); PD1; PDL1; blockade; IMMUNOGENIC CELL-DEATH; POLYMER NETWORKS; DRUG-DELIVERY; CANCER; PACLITAXEL; RESISTANCE; PHENOTYPE; HYDROGELS; BLOCKADE; VACCINES;
D O I
10.1016/j.jconrel.2022.04.015
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Tumor recurrence and metastasis after surgery remain challenges for tumor treatment. Strategy that can promote the immunogenicity, activate adaptative immune response and eliminate post-operative immunosuppression would be a promising way to achieve a desired clinical benefit. In this study, immunogenic cell death (ICD) priming anti-tumor adaptive immune response was executed to potentiate immune checkpoint blockade (ICB) therapy through the PD1/PDL1 pathway for postsurgical treatment. Here, we present a bio-responsive and cargocatchable gel depot composed of pullulan and chitosan cross-linking through matrix metalloproteinase (MMP) sensitive peptide for co-delivery of anti-programmed death-ligand 1 antibody (aPDL1) and doxorubicin -encapsulated liposomes (DOX-Lip). This drug carrier showed expected ability to respond to the highly expressed MMP in postsurgical tumor microenvironment (TME). In vivo studies on 4T1 breast tumor mouse model demonstrated that the gel depot could efficiently prolong the mouse survival after tumor resection by preventing tumor recurrence and metastasis. The results suggested that ICD combining with PD1/PDL1 blockade based on the bio-responsive and cargo-catchable gel depot could facilitate the maturation of DCs and reverse the immunosuppressive environment in tumor resection area, thus amplifying the systemic anti-tumor immune response.
引用
收藏
页码:212 / 225
页数:14
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