Zinc-Organometallic Framework Vaccine Controlled-Release Zn2+ Regulates Tumor Extracellular Matrix Degradation Potentiate Efficacy of Immunotherapy

Ding, Lin1,2,3; Liang, Minli1,2,3; Li, Yuanyuan4; Zeng, Mei5; Liu, Meiting5; Ma, Wei2,3; Chen, Fuming2,3; Li, Chenchen6,7; Reis, Rui L.8; Li, Fu-Rong1,2,3; Wang, Yanli6,7

2023-07-01

10.1002/advs.202302967

ADVANCED SCIENCE   影响因子和分区

2198-3844

Tumor extracellular matrix (ECM) not only forms a physical barrier for T cells infiltration, but also regulates multiple immunosuppressive pathways, which is an important reason for immunotherapy failure. The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway plays a key role in activating CD8(+) T cells, maintaining CD8(+) T cells stemness and enhancing the antitumor effect. Herein, a zinc-organometallic framework vaccine (ZPM@OVA-CpG) prepared by self-assembly, which achieves site-directed release of Zn2+ in dendritic cell (DC) lysosomes and tumor microenvironment under acidic conditions, is reported. The vaccine actively targets DC, significantly enhances cGAS-STING signal, promotes DC maturation and antigen cross-presentation, and induces strong activation of CD8(+) T cells. Meanwhile, the vaccine reaches the tumor site, releasing Zn2+, significantly up-regulates the activity of matrix metalloproteinase-2, degrades various collagen components of tumor ECM, effectively alleviates immune suppression, and significantly enhances the tumor infiltration and killing of CD8(+) T cells. ZPM@OVA-CpG vaccine not only solves the problem of low antigen delivery efficiency and weak CD8(+) T cells activation ability, but also achieves the degradation of tumor ECM via the vaccine for the first time, providing a promising therapeutic platform for the development of efficient novel tumor vaccines.

immunotherapy tumor extracellular matrix vaccine zinc-organometallic framework Zn2+

SCI ; EI

英语

第一 ; 通讯

Shenzhen Science and Technology Program[RCBS20210609104513023] ; Guangdong Basic and Applied Basic Research Foundation["2022A1515010056","2021A1515110657"] ; National Key Research and Development Program of China[2022YFC2305000] ; National Natural Science Foundation of China[82001755]

Chemistry ; Science & Technology - Other Topics ; Materials Science

Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:001024342000001

WILEY

20232914402674

Antigens ; Chemical activation ; Cytology ; Interferons ; Organometallics ; T-cells ; Vaccines ; Zinc

Biological Materials and Tissue Engineering:461.2 ; Medicine and Pharmacology:461.6 ; Biology:461.9 ; Immunology:461.9.1 ; Zinc and Alloys:546.3 ; Chemical Reactions:802.2 ; Chemical Products Generally:804 ; Organic Compounds:804.1

Web of Science

1.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp, Shenzhen 518055, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp, Translat Med Collaborat Innovat Ctr, Shenzhen 518020, Peoples R China
3.Guangdong Engn Technol Res Ctr Stem Cell & Cell Th, Shenzhen Immune Cell Therapy Publ Serv Platform, Shenzhen Key Lab Stem Cell Res & Clin Transformat, Shenzhen 518020, Peoples R China
4.Jiaozuo Womens & Childs Hosp, Clin Lab, Jiaozuo 454001, Peoples R China
5.Guangdong Med Univ, Sch Pharm, Dongguan 523109, Peoples R China
6.Hainan Med Univ, Sch Pharm, Minist Educ, Key Lab Trop Translat Med, Haikou 570228, Peoples R China
7.Hainan Med Univ, Affiliated Hosp 1, Haikou 570228, Peoples R China
8.Univ Minho, I3Bs Res Inst Biomat Biodegradables & Biomimet, 3Bs Res Grp, P-4805017 Guimaraes, Portugal

Ding, Lin,Liang, Minli,Li, Yuanyuan,et al. Zinc-Organometallic Framework Vaccine Controlled-Release Zn2+ Regulates Tumor Extracellular Matrix Degradation Potentiate Efficacy of Immunotherapy[J]. ADVANCED SCIENCE,2023,10(27).

Ding, Lin.,Liang, Minli.,Li, Yuanyuan.,Zeng, Mei.,Liu, Meiting.,...&Wang, Yanli.(2023).Zinc-Organometallic Framework Vaccine Controlled-Release Zn2+ Regulates Tumor Extracellular Matrix Degradation Potentiate Efficacy of Immunotherapy.ADVANCED SCIENCE,10(27).

Ding, Lin,et al."Zinc-Organometallic Framework Vaccine Controlled-Release Zn2+ Regulates Tumor Extracellular Matrix Degradation Potentiate Efficacy of Immunotherapy".ADVANCED SCIENCE 10.27(2023).