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

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. Contrastenhanced 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, dualmodality 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 dualmode imaging, and precise cascade treatment. This unique theranostic NPS with multiple capabilities is expected to be a favourable anti-cancer method in the future.

Necropotosis-Induciable Nanoliposomes for Enhanced Cancer Sonoimmunotherapy in Vitro

“…The liposomes were synthesized using a two-step emulsion method. 31 Transmission electron microscopy demonstrated a nearly spherical structure of lip-ICG-PFP and Lip-ICG-PFP-cRGD with smooth surfaces (Figs. 1A and B).…”

Single-cell RNA sequencing reveals the mechanism of sonodynamic therapy combined with a RAS inhibitor in the setting of hepatocellular carcinoma

“…Several reports have shown that LIFU could enhance the drug sensitivity of some select chemotherapeutic drugs and could improve cell membrane permeability [ 33 – 35 ]. Our previous research showed that the combination of LIFU exposure and the nanobubble system can be used as an efficient and safe approach for gene delivery and transfection [ 36 , 37 ].…”

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

“…The generation of ROS during this process induces cytotoxicity toward cancer cells effectively, leading to rapid DNA damage and apoptosis of tumor cells [9]. Unlike the super cial employment of photodynamic therapy (PDT), SDT receives a more pleasant therapeutic outcome in treating deep-seated tumors by low intensity focused ultrasound (LIFU) which owns merits to prevent undesirable thermal injury during treatment [11][12][13]. As one of the essentials in SDT, sonosensitizers have been explored in various tumor therapies [14].…”