Ultrasound-Mediated Cavitation Enhances EGFR-Targeting PLGA-PEG Nano-Micelle Delivery for Triple-Negative Breast Cancer Treatment

超声介导的空化作用增强了 EGFR 靶向 PLGA-PEG 纳米胶束输送,用于三阴性乳腺癌治疗

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作者:Libin Chen, Tao Zhang, Shan Sun, Wenzhi Ren, Aiguo Wu, Huixiong Xu

Abstract

Triple-negative breast cancer (TNBC) is highly recurring and metastatic breast cancer with overexpressing epidermal growth factor receptor (EGFR). Herein, a series of in vitro and in vivo analyses were used to explore the therapeutic effect of EGFR-targeting nano-micelles (PLGA-PEG/DOX@anti-EGFR) combined with ultrasound-mediated cavitation (UMC). The prepared nano-micelle drug carriers have good biocompatibility and can greatly increase the drug accumulation in tumor regions, thereby reducing off-target toxicity while enhancing anti-tumor efficacy. Moreover, an in vivo analysis of the practical utility of this treatment modality was conducted by using SonoVueTM microbubbles to achieve cavitation under different power intensity levels, with an ultrasonic power intensity of 0.5 W/cm2 maximizing the intra-tumoral blood perfusion. Relative to PLGA-PEG@DOX/anti-EGFR nano-micelles treatment alone, the combination with UMC was better able to suppress tumor growth even at low concentrations. As such, combining actively targeted drug-carrier molecules with UMC represents an effective approach to enhancing therapeutic efficacy while reducing the adverse, systemic effects associated with DOX and other chemotherapeutic drugs, and it can be considered as a promising clinical prospect in the treatment of TNBC.

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