Low-Intensity Focused Ultrasound-Augmented Multifunctional Nanoparticles for Integrating Ultrasound Imaging and Synergistic Therapy of Metastatic Breast Cancer

Qian Zhang,Hongyu Tao,Wen Wang,Chenyu Wang,Jiaxing Wang,Chengrong Mi,Yating Wu,Furong Zhang,Hongyuan Shen,Ruijiao Chang,Hanfei Zhang,Guangfei Yang,Jiaojiao Qi,Liyuan Ma

doi:10.1186/s11671-021-03532-z

Abstract

The metastasis of breast cancer is believed to have a negative effect on its prognosis. Benefiting from the remarkable deep-penetrating and noninvasive characteristics, sonodynamic therapy (SDT) demonstrates a whole series of potential leading to cancer treatment. To relieve the limitation of monotherapy, a multifunctional nanoplatform has been explored to realize the synergistic treatment efficiency. Herein, we establish a novel multifunctional nano-system which encapsulates chlorin e6 (Ce6, for SDT), perfluoropentane (PFP, for ultrasound imaging), and docetaxel (DTX, for chemotherapy) in a well-designed PLGA core–shell structure. The synergistic Ce6/PFP/DTX/PLGA nanoparticles (CPDP NPs) featured with excellent biocompatibility and stability primarily enable its further application. Upon low-intensity focused ultrasound (LIFU) irradiation, the enhanced ultrasound imaging could be revealed both in vitro and in vivo. More importantly, combined with LIFU, the nanoparticles exhibit intriguing antitumor capability through Ce6-induced cytotoxic reactive oxygen species as well as DTX releasing to generate a concerted therapeutic efficiency. Furthermore, this treating strategy actives a strong anti-metastasis capability by which lung metastatic nodules have been significantly reduced. The results indicate that the SDT-oriented nanoplatform combined with chemotherapy could be provided as a promising approach in elevating effective synergistic therapy and suppressing lung metastasis of breast cancer.

Highlights

Breast cancer has haunted women for years as one of the most threatening malignant tumors
Characterization of CPDP PFP/DTX/PLGA nanoparticles (NPs) and Drug‐Releasing Efficiency A double emulsion method was applied in fabricating CPDP NPs, which encapsulated both phase-shift material PFP, sonosensitizer Chlorine e6 (Ce6), and chemo-drug DTX simultaneously
The size of CPDP NPs guaranteed that it could be accumulated into the tumor site passively through the enhanced permeability and retention (EPR) effect [40]

Summary

Introduction

Breast cancer has haunted women for years as one of the most threatening malignant tumors. Due to the high heterogeneity and high metastatic ability, it is reported that the distant metastasis of breast cancer accounted for Traditional therapeutic approaches such as surgery and chemotherapy are still considered to be effective in treating breast cancer [4]. Zhang et al Nanoscale Res Lett (2021) 16:73 drugs, docetaxel (DTX) is playing a significant role in treating metastatic breast cancer (MBC) and advanced breast cancer (ABC) [5]. Owning to its extensive antitumor efficiency, DTX is becoming one of the most effective chemotherapeutic agents in treating breast cancer [7]. Chemotherapy agent usually induces undesirable effects as well as whole-body toxicity, which have restricted the therapeutic efficiency greatly [8]. Different clinical stages and various personal conditions reveal that a single therapeutic approach may not be efficient enough to meet all the expectations in breast cancer treatment. There is an urgent need to curb the toxic side effect and enhance treating effectiveness of DTX in the future application requirements

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Conclusion