Deciphering single-cell transcriptomic landscape of tumors in colorectal cancer treated with photothermal semiconducting polymers to design the combination therapy with checkpoint blockades for inhibition of tumor progression and metastasis

Yuan, Haitao1; Bai, Yunmeng1; Gu, Di1,2; Wang, Peili1,3; Sun, Xin1; Yang, Jing1; Wong, Yin Kwan4; Huang, Wei5; Wang, Xiaoxian1; Ma, Jingbo1; Dong, Zhiyu1; Chen, Ruixing6; Li, Jiexuan1; Li, Zhijie1; Zeng, Guohua1,2; Gong, Zipeng1,6; Yang, Chuanbin1; Wang, Jigang1,2,7,8,9

2024-10-01

10.1016/j.nantod.2024.102419

NANO TODAY   影响因子和分区

1748-0132

1878-044X

Immunotherapy is often less effective for tumors with "immune-excluded," or "immune-desert" microenvironment. To circumvent this hurdle, new therapeutic strategies need to be designed to reprogram the tumor microenvironment (TME). It is well known that photothermal therapy (PTT) can prime the TME and provoke the systemic anti-tumor immunity. But few studies perform extensive exploration in depth to decipher the changes in TME after PTT with cutting-edge technology besides conventional flow cytometry analysis. In this study, we designed a nanosystem consisting of organic semiconductor polymer liposome nanoparticles (Y8 NPs) as a multimodal imaging and photothermal agent to image and treat tumors. Upon laser irradiation, Y8 NPs in tumors could rapidly increase the temperature, induce massive cancer cell apoptosis and also promote the immunogenic cell death (ICD), ultimately remodulating the TME. We employed single cell RNA sequencing (scRNA-seq) technology to comprehensively explore transcriptomic profiling of individual cells constituting TME, demonstrating heterogenous alterations in the subtypes of immune cells, even tumor cells. Considering the findings by scRNA-seq and TME remodulation, the combinational strategy with checkpoint blockade PD-1 antibody was designed to treat the tumors, demonstrating that the combination not only impedes primary tumor progression but also produce profound abscopal anti-tumor effect. In conclusion, we provide a simple strategy for the remodulation of TME with a photothermal nanosystem to achieve activation of anti-tumor immunity, and suppress primary and metastatic tumor progression.

Immunogenic cell death Single-cell transcriptomic landscape Immunotherapy

SCI ; EI

英语

第一 ; 通讯

National Key Research and Development Program of China["2022YFC2303600","2020YFA0908000"] ; Scientific and technological innovation project of China Academy of Chinese Medical Sciences["CI2023D003","CI2023D008","CI2021B014"] ; CACMS Innovation Fund["CI2023E002","CI2021A05101","CI2021A05104"] ; Science and Technology Foundation of Shenzhen["JCYJ20210324115800001","JCYJ20210324113608023"] ; Shenzhen Medical Research Fund[B2302051] ; Shenzhen Governmental Sustainable Development Fund[KCXFZ20201221173612034] ; Shenzhen Fund for Guangdong Provincial High- level Clinical Key Specialties[SZGSP001] ; Shenzhen Science and Technology Innovation Commission["JCYJ20200109120205924","JCYJ20210324114202008"] ; Guang Dong Basic and Applied Basic Research Foundation["2021A1515012164","2022A1515110745"] ; International Science and Technology Cooperation for Shenzhen Technology Innovation Plan[GJHZ20200731095411034] ; Chinese Postdoctoral Science Foundation[2022M712190] ; Key Special Project of "Strategic Science and Technology Innovation Cooperation" from National Key R & D Program of China[2023YFE0204500] ; Shenzhen Science and Technology Innovation Committee (SZSTI)[RCYX20221008092950121] ; National Natural Science Foundation of China["82373775","82070517"]

Chemistry ; Science & Technology - Other Topics ; Materials Science

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

WOS:001290903400001

ELSEVIER SCI LTD

Web of Science

1.Southern Univ Sci & Technol, Guangdong Prov Clin Res Ctr Geriatr, Shenzhen Clin Res Ctr Geriat, Shenzhen Peoples Hosp,Clin Med Coll 2,Jinan Univ,A, Shenzhen 518020, Guangdong, Peoples R China
2.Guangzhou Med Univ, Guangdong Key Lab Urol, Affiliated Hosp 1, Guangzhou 510230, Guangdong, Peoples R China
3.China Acad Chinese Med Sci, Xiyuan Hosp, Natl Clin Res Ctr Chinese Med Cardiol, Beijing, Peoples R China
4.Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Physiol Sci, Singapore 117600, Singapore
5.Sun Yat Sen Univ, Sch Chem Engn & Technol, Zhuhai 519082, Peoples R China
6.Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guizhou Prov Key Lab Pharmaceut, Guiyang 550004, Peoples R China
7.Henan Univ, Sch Pharm, State Key Lab Antiviral Drugs, Kaifeng 475004, Peoples R China
8.China Acad Chinese Med Sci, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China
9.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China

Yuan, Haitao,Bai, Yunmeng,Gu, Di,et al. Deciphering single-cell transcriptomic landscape of tumors in colorectal cancer treated with photothermal semiconducting polymers to design the combination therapy with checkpoint blockades for inhibition of tumor progression and metastasis[J]. NANO TODAY,2024,58.

Yuan, Haitao.,Bai, Yunmeng.,Gu, Di.,Wang, Peili.,Sun, Xin.,...&Wang, Jigang.(2024).Deciphering single-cell transcriptomic landscape of tumors in colorectal cancer treated with photothermal semiconducting polymers to design the combination therapy with checkpoint blockades for inhibition of tumor progression and metastasis.NANO TODAY,58.

Yuan, Haitao,et al."Deciphering single-cell transcriptomic landscape of tumors in colorectal cancer treated with photothermal semiconducting polymers to design the combination therapy with checkpoint blockades for inhibition of tumor progression and metastasis".NANO TODAY 58(2024).