<p>A Cleverly Designed Novel Lipid Nanosystem: Targeted Retention, Controlled Visual Drug Release, and Cascade Amplification Therapy for Mammary Carcinoma in vitro</p>
Authors: Xing-Yue Wang
Shuai-Shuai Huang
Hai-Tao Ran
Dan Guo
Yi-Zhen Li
Wei Zhang
Xiang-Zhi Zhao
Yang Cao
Journal: International Journal of Nanomedicine (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: AQ4N; HMME; LIFU; SDT.
Affiliations: Ultrasound Department of the Second Affiliated Hospital of Chongqing Medical University, Chongqing Key Laboratory of Ultrasound Molecular Imaging, Chongqing 400016, People's Republic of China., Department of Cardiovascular Ultrasound, Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan Province, People's Republic of China., Ultrasound Department, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, People's Republic of China., Department of Renal Disease, Urology and Nephrology Hospital of Ningbo University, Ningbo 315100, Zhejiang, People's Republic of China., Department of Cardiovascular Ultrasound and Noninvasive Cardiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, People's Republic of China.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Figure 3A. Much more similar than expected. https: imgur.com R0XjciM , 
 WB smiles in a different direction for the actin replacement panel and lane widths do not match. ,