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

Weiwei Liu,Lu Yang,Juan Cheng,Wei Zhang,Min Zheng,Lingyun He,Yang Cao,Yaqin Hu,Wenpei Luo,Xiaoping Ye,Haitao Ran

doi:10.1186/s12951-021-01186-8

Abstract

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

Highlights

Breast cancer remains one of the gravest and lethal diseases that seriously threaten women’s health nowadays, whose incidence has surpassed that of lung cancer and ranked first among all tumors in 2020 [1,2,3]
Distant metastasis in breast cancer mainly occurs in vital organs including liver, lung and brain through the regional lymph node metastasis, which is the primary cause of mortality [4,5,6,7]
HPDC NPs accumulated at metastatic lymph node sites via passive targeting by lymphatic injection and intracellular targeting at HIF 1α factor mediated by anti-HIF 1α antibody

Summary

Introduction

Breast cancer remains one of the gravest and lethal diseases that seriously threaten women’s health nowadays, whose incidence has surpassed that of lung cancer and ranked first among all tumors in 2020 [1,2,3]. Using multimodal imaging for the precise visualization of metastatic lymph nodes [27,28,29], we aimed to achieve multimodal imaging guided synergistic chemo-hyperthermia therapy and evaluation of therapeutic effect [30, 31]. Lymphatic injection-mediated passive targeting combined with antibody-mediated intracellular targeting can achieve precision therapy at the cellular level [32, 33]. We expect that this new therapeutic modality and route of administration will effectively avoid the adverse effects of surgery, chemotherapy, and radiotherapy. 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

Objectives

Results

Conclusion