IntroductionMedullary thyroid carcinoma (MTC) is an aggressive neuroendocrine malignancy with limited diagnostic strategies and inherent resistance to conventional therapies. Novel multifunctional Nanotheranostics are urgently needed to improve MTC treatment outcomes. This study aimed to construct a low-intensity focused ultrasound (LIFU)-responsive biomimetic nanoparticle system integrating multiple therapeutic modalities and dual-modal imaging for in vitro combined treatment of MTC.MethodsA tumor cell membrane-camouflaged lipid nanoparticle (MHGA@P-LNs) was fabricated to co-load hematoporphyrin monomethyl ether (HMME), glucose oxidase (GOx), AQ4N, and perfluorohexane (PFH). In vitro assays characterized physicochemical properties, LIFU responsiveness, cellular uptake, reactive oxygen species production, cytotoxicity, apoptosis, migration, and hemocompatibility. All experiments were repeated in triplicate (n = 3).ResultsMHGA@P-LNs exhibited a uniform core-shell morphology, favorable colloidal stability, and high drug encapsulation efficiency. Under LIFU irradiation, the system generated ultrasound/photoacoustic signals, increased intracellular ROS-associated fluorescence, and enhanced uptake by MZ-CRC-1 cells. Cell viability decreased to 0.9%, the total apoptosis rate reached 86.8%, and wound closure was 3.7%. The hemolysis rate remained below 3% in a mouse red blood cell assay. These results are limited to the in vitro experimental conditions.ConclusionThe in vitro data support further investigation of MHGA@P-LNs as a LIFU-responsive, image-guided combination-therapy platform for medullary thyroid carcinoma. The present findings do not establish in vivo tumor accumulation, prolonged circulation, immune evasion, metastatic targeting, systemic safety, or clinical translatability; these outcomes require dedicated animal studies.
