A novel targeted multifunctional nanoplatform for visual chemo-hyperthermia synergy therapy on metastatic lymph nodes via lymphatic delivery

Journal of Nanobiotechnology

Xiaoping Ye¹  Lingyun He¹  Min Zheng¹  Wei Zhang¹  Yang Cao¹  Weiwei Liu¹  Juan Cheng¹  Haitao Ran¹  Yaqin Hu¹  Lu Yang²  Wenpei Luo² 

[1] Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, 400010, Chongqing, People’s Republic of China;Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, 400010, Chongqing, People’s Republic of China;Department of Breast and Thyroid, The Second Affiliated Hospital of Chongqing Medical University, 400010, Chongqing, People’s Republic of China;

关键词: Carbon nanoparticles;    Metastatic lymph nodes;    Photonic hyperthermia;    Chemotherapy;    Nanomedicine;    Targeted therapy;    Molecular imaging;   

DOI  :  10.1186/s12951-021-01186-8

来源: Springer

【 摘 要 】

BackgroundDistant metastasis to vital organs is the major contributor to breast cancer mortality, and regional lymph node metastasis is an important facilitator of distant metastasis and recurrence in this cancer. The early diagnosis and precise treatment of lymph node metastasis are crucial for staging and prognosis in breast cancer. Herein, we report a visualized precision medicine nanoplatform of metastatic lymph nodes for ultrasonic/photoacoustic (US/PA) dual modal imaging-guided in situ targeted hyperthermia-combined chemotherapy.ResultsCarbon nanoparticles (CNs), approved by the China Food and Drug Administration, were loaded with docetaxel and rationally combined with anti-hypoxia-inducible factor 1α antibody-modified poly (lactic-co-glycolic acid) (PLGA) nanoparticles to achieve the combination of passive targeting at the lymph nodes and intracellular targeting at HIF 1α factor. The accumulation and retention of nanoparticles in metastatic lymph nodes via lymphatic delivery were enhanced. Docetaxel could be effectively offloaded by CNs that have active carbon nanoparticles, and the PLGA membrane prevented drug leakage. The nanoparticles exhibited excellent photothermal performance with a photothermal conversion efficiency of 28.9%, killing tumor cells in metastatic lymph nodes through hyperthermia. In vitro and in vivo systematic evaluations revealed that hyperpyrexia triggered the rupture of nanoparticles caused by the phase transition of perfluorohexane, resulting in docetaxel release for achieving in situ hyperthermia-combined chemotherapy.ConclusionsThe laser-triggered highly efficient in situ chemotherapy nanosystem achieves targeted synergistic chemo-hyperthermia treatment of metastatic lymph nodes, and lymphatic delivery represents a strategy to avoid additional injury caused by drugs entering the blood circulation.Graphical Abstract

【 授权许可】

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