作者：

Huan Ye¹, Jing Yan², Yang Zhou¹, Chenglong Ge¹, Ling Zhong³, Jie Wang⁴, Kaimin Cai⁵, Jianjun Cheng⁶, Zhuchao Zhou⁴*, and Lichen Yin¹*

单位：

¹Jiangsu Key Laboratory of Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials (FUNSOM), Collaborative Innovation Center of Suzhou Nano Science & Technology, Soochow University, Suzhou, China

²Department of Gastroenterology, The Second Affiliated Hospital of Soochow University, Suzhou, China

³Amsterdam University College, University of Amsterdam and Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

⁴Department of Breast Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

⁵Department of Materials Science and Engineering University of Illinois at Urbana-Champaign Urbana, Urbana, Illinois, USA

⁶School of Engineering, Westlake University, Hangzhou, China

摘要：

Tumor-surface antigen deficiency and immunosuppressive tumor microenvironment (TME) hurdle the efficacy of antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells. Here, acid-activatable, polypeptide-basednano-haptens are developed and coupled with glycometabolism-mediated tumor labeling to potentiate NK cell-mediated ADCC. The nano-haptens comprise chemotactic peptide (WKYMVm)-encapsulated hollow mesoporous silica nanoparticles(HMSNs) that are shelled by conformation-transformable polypeptides containing conjugated dibenzocyclooctyne (DBCO) anddinitrophenyl derivative (FDNB) at the backbone termini. In tumor-bearing mice, an unnatural sugar (DCL-AAM) was used toglycometabolically label tumor cell surfaces with azido groups, followed by systemic administration of the nano-haptens. During blood circulation, the negatively charged, random-coiled polypeptides flatly stack on the HMSN surface, preventing WKYMVm leakage and shielding the FDNB and DBCO domains. Inside the acidic TME, the polypeptides transform into positively charged,rigid α-helices, unmasking the pores and releasing WKYMVm to enhance intratumoral infiltration of NK cells. Concurrently,DBCO and FDNB are conditionally exposed to enable anchoring of nano-haptens onto azido-labeled tumor cells and binding of endogenous anti-dinitrophenyl, respectively, thereby bridging tumor cells and NK cells to assist robust ADCC. When further coupled with anti-Ly49C that ameliorates the immunosuppressive TME, the nano-haptens achieve potent tumor elimination and induce durable adaptive immunity to prevent tumor recurrence.

影响因子：

26.8

分区情况：

一区

链接：

https://doi.org/10.1002/adma.72782