Human epidermal growth factor receptor 2(Her2)-targeted pH-responsive MR/NIRF bimodal imaging-mediated nano-delivery system for the diagnosis and treatment of undifferentiated thyroid cancer.

Undifferentiated thyroid cancer (ATC) is highly malignant and does not respond well to sorafenib (SRF) treatment owing to the lack of specificity of SRF targeting. Drug delivery nanosystems can improve the efficiencies of drug in treating various cancer types. However, many conventional drug delivery nanosystems lack targeting and exhibit unresponsive drug release. Therefore, we developed a pH-responsive nano-targeted drug delivery systems using human serum albumin (HSA) as a carrier to generate manganese dioxide (MnO₂)@HSA nanoparticles (NPs), then encapsulated SRF and the fluorescent dye indocyanine green (ICG) and finally modifyed the targeting antibody pertuzumab in the outer layer of the nano complexes, resulting in SRF/ICG/MnO₂@HSA-pertuzumab (HISMP) NPs. This system targets human epidermal growth factor receptor 2 on the cell membrane surface of thyroid cancer cells and is designed to accumulate at tumor sites. Then, pH-responsive release of divalent manganese ions, ICG, and SRF enables magnetic resonance/fluorescence (MR/NIRF) dual-modality imaging and precise drug delivery for diagnostic and therapeutic integration. Various characterization analyses including transmission electron microscopy, Fourier infrared spectroscopy, and particle size analysis confirm that we successfully synthesized HISMP NPs with a diameter of 150.709 nm. The results of CCK8 cytotoxicity and apoptosis assays show that HISMP NPs exhibited high cytotoxicity and induce apoptosis in thyroid cancer cells. In vivo MR/NIRF imaging experiments confirmed that the HISMP NPs specifically aggregated at tumor sites and have good in vivo MR/NIRF imaging ability and effective anti-tumor activity. The nano-delivery system is expected to provide a theoretical foundation for the efficient ATC diagnosis and therapy.