SCHEDULED MAINTENANCE
Thyroid-stimulating hormone (TSH)-armed polymer–lipid nanoparticles for the targeted delivery of cisplatin in thyroid cancers: therapeutic efficacy evaluation
Abstract
Thyroid-stimulating hormone (TSH)-conjugated polymer–lipid hybrid nanoparticles (TPLHC) were developed for the targeted delivery of cisplatin (CDDP) in thyroid cancers. In the present study, polymer–lipid hybrid nanoparticles were conjugated to TSH, which will bind to the TSH receptor (TSHr) on the surface of thyrocytes. This delivery system was mainly designed to achieve high concentrations in thyroid carcinomas. The TPLHC exhibited excellent properties, which were attributed to their nanoscaled size of 160 nm with a narrow distribution to benefit EPR-based passive targeting. The polymer–lipid nanoparticle efficiently controlled the release of drugs in physiological conditions. The TSH-conjugated nanoparticles displayed higher cellular uptake in cells, which overexpress TSHr. TPLHC consistently showed high intracellular levels of CDDP in FTC-133 cancer cells. Specifically, the TSH-conjugated nanoparticles showed a significantly enhanced anticancer effect compared to the other groups across all time points and concentrations tested. In addition, a 4-fold higher accumulation of the TSH-conjugated NP was observed in tumors compared to the non-targeted NP in xenograft mice. Importantly, the TPLHC inhibited the growth of tumors more efficiently than the other formulations. This enhanced tumor inhibition might be attributed to the specific binding of TSH to the TSHr overexpressed in FTC-133 tumors. Taken together, the TSH-conjugated nanoparticles hold great potential to be an effective and safe nanoscale delivery system for the targeted therapy of thyroid cancers.
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