Novel Multifunctional Nanoagent for Visual Chemo/Photothermal Therapy of Metastatic Lymph Nodes via Lymphatic Delivery

Juan Cheng; Ying Liu; Lingyun He; Weiwei Liu; Yuli Chen; Fengqiu Liu; Yuan Guo; Haitao Ran; Lu Yang

doi:10.1021/acsomega.9b03258

Novel Multifunctional Nanoagent for Visual Chemo/Photothermal Therapy of Metastatic Lymph Nodes via Lymphatic Delivery

ACS Omega. 2020 Feb 13;5(7):3194-3206. doi: 10.1021/acsomega.9b03258. eCollection 2020 Feb 25.

Authors

Juan Cheng^{1

2}, Ying Liu³, Lingyun He⁴, Weiwei Liu^{1

2}, Yuli Chen^{1

2}, Fengqiu Liu^{1

2}, Yuan Guo^{1

2}, Haitao Ran^{1

2}, Lu Yang³

Affiliations

¹ Ultrasound Department, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
² Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing 400010, China.
³ Department of Breast and Thyroid Surgery, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
⁴ Department of Scientific Research and Education Section, Chongqing Health Center for Women and Children, Chongqing 401120, China.

Abstract

Breast cancer is one of the major diseases that threaten women's health. Lymph node (LN) metastasis is the most common metastatic path of breast cancer. Finding a simple, effective, and safe strategy to eliminate metastatic tumors in LNs is highly desired for clinical use. Carbon nanoparticles (CNs), as an LN tracer, have been widely used in the clinical setting. In addition, previous experiments have confirmed that CNs have good photoacoustic imaging and photothermal effects. In this study, we used CNs as a photothermal conversion material and drug carrier, poly(lactic-co-glycolic acid) (PLGA) as a film-forming material, and docetaxel as a chemotherapy drug to prepare multifunctional nanoparticles (DOC-CNPs). The prepared DOC-CNPs present as a black solution, which shows smooth spherical particles under light microscopy and transmission electron microscopy (TEM), and they have a good ability for liquid-gas phase transition, good dispersibility, high drug-loading capacity, and low cytotoxicity. In vitro, they can release drugs and inhibit tumor cells after laser irradiation. The photoacoustic (PA) signal intensity and the photothermal conversion efficiency increased with an increase in the concentration of DOC-CNPs. In vivo, after administration, the DOC-CNPs reached the LNs. After laser irradiation, the DOC-CNPs absorbed laser energy, and the temperature of the LNs increased high enough to achieve photothermal therapy under PA and ultrasound monitoring. Fracture of the DOC-CNPs was caused by the liquid-gas phase transition with the increased temperature, and the ruptured DOC-CNPs released docetaxel to achieve targeted chemotherapy. These findings suggested that DOC-CNPs can achieve precise treatment for metastatic LNs of breast cancer with PA and ultrasound visualization.