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Article

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

by 1,2,†, 3,†, 4, 4, 4,* and 1,5,*
1
School of Medicine, Tongji University, Shanghai 200072, China
2
Department of Ultrasound in Medicine, Ningbo First Hospital, Ningbo 315010, China
3
Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China
4
Cixi Institute of Biomedical Engineering, International Cooperation Base of Biomedical Materials Technology and Application, CAS Key Laboratory of Magnetic Materials and Devices & Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, 1219 ZhongGuan West Road, Ningbo 315201, China
5
Center of Minimally Invasive Treatment for Tumor, Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Ultrasound Research and Education Institute, Clinical Research Center for Interventional Medicine, School of Medicine, Tongji University, Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment, National Clinical Research Center for Interventional Medicine, 301 Yanchangzhong Rd, Shanghai 200072, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Samuel C. Mok
Cancers 2021, 13(14), 3383; https://doi.org/10.3390/cancers13143383
Received: 5 June 2021 / Revised: 24 June 2021 / Accepted: 26 June 2021 / Published: 6 July 2021
Triple-negative breast cancer (TNBC) with negative expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) is considered to be associated with poorer outcomes and a higher risk of recurrence or metastasis owing to a lack of effective targeted therapeutic drugs. The epidermal growth factor receptor (EGFR) functions is a driver of disease progression in most of TNBC that represents a viable target that can be leveraged to guide the intra-tumoral delivery of chemotherapeutic drugs in TNBC patients. Moreover, ultrasound-mediated cavitation (UMC) strategies increase tissue permeability and extravasation through nuclei-dependent cavitation via sonoporation, thus enabling drugs to better enter target tissues. In this research, a combination of active, targeting nano-micelles and UMC was able to inhibit TNBC tumor growth effectively at lower concentrations while reducing treatment-related toxicity. Thus, this is a very promising treatment strategy in the clinical therapy with TNBC and other cancer types.
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/[email protected]) 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 [email protected]/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. View Full-Text
Keywords: ultrasound-mediated cavitation; EGFR-targeting; triple-negative breast cancer; DOX; PLGA nano-micelle; SonoVueTM ultrasound-mediated cavitation; EGFR-targeting; triple-negative breast cancer; DOX; PLGA nano-micelle; SonoVueTM
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MDPI and ACS Style

Chen, L.; Zhang, T.; Sun, S.; Ren, W.; Wu, A.; Xu, H. Ultrasound-Mediated Cavitation Enhances EGFR-Targeting PLGA-PEG Nano-Micelle Delivery for Triple-Negative Breast Cancer Treatment. Cancers 2021, 13, 3383. https://doi.org/10.3390/cancers13143383

AMA Style

Chen L, Zhang T, Sun S, Ren W, Wu A, Xu H. Ultrasound-Mediated Cavitation Enhances EGFR-Targeting PLGA-PEG Nano-Micelle Delivery for Triple-Negative Breast Cancer Treatment. Cancers. 2021; 13(14):3383. https://doi.org/10.3390/cancers13143383

Chicago/Turabian Style

Chen, Libin, Tao Zhang, Shan Sun, Wenzhi Ren, Aiguo Wu, and Huixiong Xu. 2021. "Ultrasound-Mediated Cavitation Enhances EGFR-Targeting PLGA-PEG Nano-Micelle Delivery for Triple-Negative Breast Cancer Treatment" Cancers 13, no. 14: 3383. https://doi.org/10.3390/cancers13143383

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