PMID- 37019286 OWN - NLM STAT- MEDLINE DCOM- 20230509 LR - 20230521 IS - 1873-4995 (Electronic) IS - 0168-3659 (Linking) VI - 357 DP - 2023 May TI - Guanidine-modified nanoparticles as robust BTZ delivery carriers and activators of immune responses. PG - 310-318 LID - S0168-3659(23)00254-7 [pii] LID - 10.1016/j.jconrel.2023.04.004 [doi] AB - Dendritic cells (DCs), the primary antigen-presenting cells in the immune system, play a critical role in regulating tumor immune responses. However, the tumor immunosuppressive microenvironment severely impedes the process of antigen-presenting and DC maturation, thereby limiting the efficacy of cancer immunotherapy. In this work, a pH-responsive polymer nanocarrier (PAG) modified with aminoguanidine (AG) was constructed for the efficient delivery of bortezomib (BTZ) through bidentate hydrogen bonds and electrostatic adsorption formed between guanidine groups of PAG and boronic acid groups of BTZ. The obtained PAG/BTZ nanoparticles exhibited pH-responsive release of BTZ and AG in the acidic tumor microenvironment. On the one hand, BTZ induced potent immune activation by eliciting immunogenic cell death (ICD) and releasing damage-associated molecular patterns. On the other hand, the cationic AG significantly promoted antigen uptake by DCs and activated DC maturation. As a result, PAG/BTZ significantly stimulated tumoral infiltration of cytotoxic T lymphocytes (CTLs) and triggered robust antitumor immune responses. Thus, it showed potent antitumor efficacy when synergizing with an immune checkpoint-blocking antibody. CI - Copyright (c) 2023 Elsevier B.V. All rights reserved. FAU - Xu, Xiaodan AU - Xu X AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China; Department of Chemistry, Zhejiang University, Hangzhou 310027, China. FAU - Wang, Rui AU - Wang R AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Li, Dongdong AU - Li D AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Xiang, Jiajia AU - Xiang J AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Zhang, Wei AU - Zhang W AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Shi, Xueying AU - Shi X AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Xu, Hongxia AU - Xu H AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Yao, Shasha AU - Yao S AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Liu, Jiwei AU - Liu J AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Shao, Shiqun AU - Shao S AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Zhou, Zhuxian AU - Zhou Z AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Huang, Feihe AU - Huang F AD - Department of Chemistry, Zhejiang University, Hangzhou 310027, China. FAU - Shen, Youqing AU - Shen Y AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. FAU - Tang, Jianbin AU - Tang J AD - Zhejiang Key Laboratory of Smart Biomaterials, and College of Chemical and Biological Engineering, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou 310027, China. Electronic address: jianbin@zju.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230406 PL - Netherlands TA - J Control Release JT - Journal of controlled release : official journal of the Controlled Release Society JID - 8607908 RN - 69G8BD63PP (Bortezomib) RN - 0 (Drug Carriers) RN - JU58VJ6Y3B (Guanidine) RN - 0 (Antigens) SB - IM MH - Humans MH - Bortezomib/pharmacology MH - Drug Carriers/chemistry MH - Guanidine MH - *Neoplasms/drug therapy MH - Antigens MH - Immunity MH - *Nanoparticles/chemistry MH - Immunotherapy MH - Cell Line, Tumor MH - Tumor Microenvironment OTO - NOTNLM OT - Aminoguanidine OT - Bortezomib OT - Cancer drug delivery OT - Chemo-immunotherapy OT - Immune activation OT - Immunogenic cell death COIS- Declaration of Competing Interest The authors declare that they have no conflict of interest. EDAT- 2023/04/06 06:00 MHDA- 2023/05/09 06:42 CRDT- 2023/04/05 19:25 PHST- 2022/12/13 00:00 [received] PHST- 2023/03/09 00:00 [revised] PHST- 2023/04/02 00:00 [accepted] PHST- 2023/05/09 06:42 [medline] PHST- 2023/04/06 06:00 [pubmed] PHST- 2023/04/05 19:25 [entrez] AID - S0168-3659(23)00254-7 [pii] AID - 10.1016/j.jconrel.2023.04.004 [doi] PST - ppublish SO - J Control Release. 2023 May;357:310-318. doi: 10.1016/j.jconrel.2023.04.004. Epub 2023 Apr 6.