Cancer cell membrane-coated nanoparticles for bimodal imaging-guided photothermal therapy and docetaxel-enhanced immunotherapy against cancer

Journal of Nanobiotechnology

Zhuoyan Xie¹  Tingting Shang²  Mixiao Tan²  Wei Zhang²  Yang Cao²  Qiaoqi Chen²  Weiwei Liu²  Haitao Ran²  Lin Li²  Zhigang Wang²  Liang Zhang³  Shuling Liu⁴ 

[1] Chongqing General Hospital, University of Chinese Academy of Sciences, No.114 Longshan Road, Yubei District, 401121, Chongqing, People’s Republic of China;Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, 400010, Chongqing, People’s Republic of China;Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, The Second Affiliated Hospital, Chongqing Medical University, No.76 Linjiang Road, Yuzhong District, 400010, Chongqing, People’s Republic of China;Department of Ultrasound, The First Affiliated Hospital, Chongqing Medical University, No.1 Youyi Road, Yuzhong District, 400042, Chongqing, People’s Republic of China;Department of Radiology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, No. 181 Hanyu Road, Shapingba District, 400030, Chongqing, People’s Republic of China;

关键词: Cocktail therapy;    Photothermal therapy;    Immunosuppressive tumor microenvironment;    Homologous targeting;    Nanomedicine;   

DOI  :  10.1186/s12951-021-01202-x

来源: Springer

【 摘 要 】

BackgroundMono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer.ResultsPoly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated “M@P-PDR”), which acted as “Nano-targeted cells” to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with “Nano-targeted cells”-based cocktail therapy.Conclusion“Nano-targeted cells”-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence.Graphical Abstract

【 授权许可】

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