Nanoengineered CAR-T Biohybrids for Solid Tumor Immunotherapy with Microenvironment Photothermal-Remodeling Strategy

Chen，Ze1; Pan，Hong1; Luo，Yingmei2; Yin，Ting2; Zhang，Baozhen1; Liao，Jianhong1; Wang，Mengmeng1; Tang，Xiaofan1; Huang，Guojun1; Deng，Guanjun1; Zheng，Mingbin1,2,3,4; Cai，Lintao1,4

2021

10.1002/smll.202007494

Small   影响因子和分区

1613-6810

1613-6829

Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable clinical success in eradicating hematologic malignancies. However, hostile microenvironment in solid tumors severely prevents CAR-T cells migrating, infiltrating, and killing. Herein, a nanoengineered CAR-T strategy is reported for enhancing solid tumor therapy through bioorthogonal conjugation with a nano-photosensitizer (indocyanine green nanoparticles, INPs) as a microenvironment modulator. INPs engineered CAR-T biohybrids (CT-INPs) not only retain the original activities and functions of CAR-T cells, but it is further armed with fluorescent tracing and microenvironment remodeling abilities. Irradiated with laser, CT-INPs demonstrate that mild photothermal intervention destroys the extracellular matrix, expanded blood vessels, loosened compact tissue, and stimulated chemokine secretion without damping CAR-T cell activities. Those regulations induce an immune-favorable tumor microenvironment for recruitment and infiltration of CT-INPs. CT-INPs triggered photothermal effects collapse the physical and immunological barriers of solid tumor, and robustly boosted CAR-T immunotherapy. Therefore, CAR-T biohybrids provide reliable treatment strategy for solid tumor immunotherapy via microenvironment reconstruction.

bioactive material chimeric antigen receptor T cell therapy microenvironment remodeling physiologic barrier solid tumor

SCI ; EI

英语

其他

National Natural Science Foundation of China[81971749,81901864,81701816,21701033,32000982] ; National Key Research and Development Program of China[2019YFE0198700] ; Guangdong Provincial Key Area RD Program[2020B1111540001] ; Natural Science Foundation of Guangdong Province["2017A030313079","2017A030313726","2019A1515011524"] ; K.C. Wong Education Foundation[GJTD-2018-14] ; Shenzhen Science and Technology Program["JCYJ20200109114616534","JCYJ20170818162259843"] ; China Postdoctoral Science Foundation["2018M640841","2019M660219"] ; Special Research Assistant Project of the Chinese Academy of Sciences[Y959101001] ; Guang dong Basic and Applied Basic Research Fund Project[2019A1515110222] ; Zhuhai Innovation and Entrepreneurship Team Project[ZH01110405180056PWC]

Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics

Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter

WOS:000627916100001

WILEY-V C H VERLAG GMBH

20211110077429

Blood vessels ; Cytology ; Photosensitizers ; T-cells

Biological Materials and Tissue Engineering:461.2 ; Immunology:461.9.1 ; Light/Optics:741.1

2-s2.0-85102380541

Scopus

1.Guangdong Key Laboratory of Nanomedicine,CAS-HK Joint Lab for Biomaterials,Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations,Shenzhen Institutes of Advanced Technology (SIAT),Chinese Academy of Sciences,Shenzhen,518055,China
2.Guangdong Key Laboratory for Research and Development of Natural Drugs,Guangdong Medical University,Dongguan,523808,China
3.National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,The Second Affiliated Hospital,Southern University of Science and Technology,Shenzhen,518112,China
4.Medical Device Research and Development Center,Zhuhai Institute of Advanced Technology Chinese Academy of Sciences,Zhuhai,519000,China

Chen，Ze,Pan，Hong,Luo，Yingmei,et al. Nanoengineered CAR-T Biohybrids for Solid Tumor Immunotherapy with Microenvironment Photothermal-Remodeling Strategy[J]. Small,2021,17(14).

Chen，Ze.,Pan，Hong.,Luo，Yingmei.,Yin，Ting.,Zhang，Baozhen.,...&Cai，Lintao.(2021).Nanoengineered CAR-T Biohybrids for Solid Tumor Immunotherapy with Microenvironment Photothermal-Remodeling Strategy.Small,17(14).

Chen，Ze,et al."Nanoengineered CAR-T Biohybrids for Solid Tumor Immunotherapy with Microenvironment Photothermal-Remodeling Strategy".Small 17.14(2021).