In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment

被引：861

作者：

Chen, Qian ^{[1
,2
,3
,4
]}

Wang, Chao ^{[3
,4
]}

Zhang, Xudong ^{[1
,2
]}

Chen, Guojun ^{[1
,2
]}

Hu, Quanyin ^{[1
,2
,3
,4
]}

Li, Hongjun ^{[5
,6
]}

Wang, Jinqiang ^{[3
,4
]}

Wen, Di ^{[1
,2
]}

Zhang, Yuqi ^{[3
,4
]}

Lu, Yifei ^{[3
,4
,7
]}

Yang, Guang ^{[1
,2
]}

Jiang, Chen ^{[7
]}

Wang, Jun ^{[5
,6
]}

Dotti, Gianpietro ^{[8
]}

Gu, Zhen ^{[1
,2
,3
,4
,9
,10
]}

机构：

[1] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Calif NanoSyst Inst, Los Angeles, CA 90095 USA

[3] Univ N Carolina, Joint Dept Biomed Engn, Chapel Hill, NC 27515 USA

[4] North Carolina State Univ, Raleigh, NC 27695 USA

[5] South China Univ Technol, Natl Engn Res Ctr Tissue Restorat & Reconstruct, Guangzhou, Guangdong, Peoples R China

[6] South China Univ Technol, Sch Biomed Sci & Engn, Guangzhou, Guangdong, Peoples R China

[7] Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Dept Pharmaceut,Minist Educ,State Key Lab Med Neu, Shanghai, Peoples R China

[8] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA

[9] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA

[10] Univ Calif Los Angeles, Ctr Minimally Invas Therapeut, Los Angeles, CA 90095 USA

来源：

NATURE NANOTECHNOLOGY | 2019年 / 14卷 / 01期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

TUMOR-ASSOCIATED MACROPHAGES; PHOTOTHERMAL THERAPY; POLARIZATION; BLOCKADE; CD47; PROMOTE; NANOPARTICLES; INFLAMMATION; METASTASIS; ACTIVATION;

D O I：

10.1038/s41565-018-0319-4

中图分类号：

TB3 [工程材料学];

学科分类号：

0805 ; 080502 ;

摘要：

Cancer recurrence after surgical resection remains a significant cause of treatment failure. Here, we have developed an in situ formed immunotherapeutic bioresponsive gel that controls both local tumour recurrence after surgery and development of distant tumours. Briefly, calcium carbonate nanoparticles pre-loaded with the anti-CD47 antibody are encapsulated in the fibrin gel and scavenge H+ in the surgical wound, allowing polarization of tumour-associated macrophages to the M1-like phenotype. The released anti-CD47 antibody blocks the 'don't eat me' signal in cancer cells, thereby increasing phagocytosis of cancer cells by macrophages. Macrophages can promote effective antigen presentation and initiate T cell mediated immune responses that control tumour growth. Our findings indicate that the immunotherapeutic fibrin gel 'awakens' the host innate and adaptive immune systems to inhibit both local tumour recurrence post surgery and potential metastatic spread.

引用

页码：89 / +

页数：10

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