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A Cleverly Designed Novel Lipid Nanosystem: Targeted Retention, Controlled Visual Drug Release, and Cascade Amplification Therapy for Mammary Carcinoma in vitro

Authors Zhao XZ, Zhang W, Cao Y, Huang SS, Li YZ, Guo D, Wang XY, Ran HT

Received 4 January 2020

Accepted for publication 5 May 2020

Published 3 June 2020 Volume 2020:15 Pages 3953—3964

DOI https://doi.org/10.2147/IJN.S244743

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Linlin Sun


Xiang-Zhi Zhao, 1, 2 Wei Zhang, 1 Yang Cao, 1, 3 Shuai-Shuai Huang, 4 Yi-Zhen Li, 5 Dan Guo, 1 Xing-Yue Wang, 1 Hai-Tao Ran 1, 3

1Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing 400016, People’s Republic of China; 2Department of Cardiovascular Ultrasound, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, People’s Republic of China; 3Ultrasound Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People’s Republic of China; 4Department of Renal Disease, Urology and Nephrology Hospital of Ningbo University, Ningbo 315100, Zhejiang, People’s Republic of China; 5Department of Cardiovascular Ultrasound and Noninvasive Cardiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan 610072, People’s Republic of China

Correspondence: Hai-Tao Ran
Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University,  No. 76, Linjiang Road, Chongqing, Yuzhong District 400010, People’s Republic of China
Email ranhaitao@cqmu.edu.cn

Objective: To construct an ideal theranostic nanoplatform (LIP3); to clarify its physicochemical properties; to confirm its characteristics of dual-modality imaging, active-targeting, and cascade amplification therapy for mammary carcinoma; and to perform a preliminary exploration of the cytotoxicity mechanism.
Design: A self-prepared liposome nanosystem, LIP3, can actively target 4T1 cells because the surface is linked with C-RGD. Haematoporphyrin monomethyl ether (HMME), an excellent sonosensitizer entrapped in the lipid bilayer, can function in photoacoustic imaging. Low-intensity focused ultrasound (LIFU) of ultrasound-targeted microbubble destruction (UTMD) promotes localized drug delivery into tumours because PFH, a phase-change substance, is loaded in the LIP3 core, achieving visualization of targeted drug release, and sonodynamic therapy (SDT) can kill tumour cells. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging and precise treatment.
Results: The self-prepared lipid nanosystem, LIP3, meets the above expectations and has ideal physicochemical properties, with a regular sphere with uniform distribution. Contrast-enhanced ultrasound (CEUS), photoacoustic imaging, and bimodal imaging were effective in vitro. In 4T1 cell experiments, the cell capacity was as high as 42.9%, and the cytotoxicity to 4T1 was more than 5 times that of LIP1 (containing AQ4N only) and more than 2 times that of LIP2 (containing only HMME), achieving comparable results as cascade therapy for mammary cancer.
Conclusion: LIP3, a theranostic nanoplatform, was successfully constructed and conformed to the physicochemical characterization of ideal nanoparticles, with active-targeting, dual-modality imaging, visualized drug release, and precise treatment under the action of LIFU. SDT provides a favourable environment for AQ4N, resulting in amplification of LIP3 treatment. Therefore, LIP3 shows targeted aggregation and targeted release, integrating dual-mode imaging, and precise cascade treatment. This unique theranostic NPS with multiple capabilities is expected to be a favourable anti-cancer method in the future.

Keywords: LIFU, SDT, HMME, AQ4N

Corrigendum for this paper has been published

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