Core‑shell type thermo‑nanoparticles loaded with temozolomide combined with photothermal therapy in melanoma cells

载有替莫唑胺的核壳型热纳米粒子联合光热疗法治疗黑色素瘤细胞

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Abstract

A novel core‑shell type thermo‑nanoparticle (CSTNP) co‑loaded with temozolomide (TMZ) and the fluorescein new indocyanine green dye IR820 (termed IT‑CSTNPs) was designed and combined with a near‑infrared (NIR) laser to realize its photothermal conversion. The IT‑CSTNPs were prepared using a two‑step synthesis method and comprised a thermosensitive shell and a biodegradable core. IR820 and TMZ were entrapped in the shell and the core, respectively. Dynamic light scattering results demonstrated that the average hydrodynamic size of the IT‑CSTNPs was 196.4±3.1 nm with a ζ potential of ‑24.9±1.3 mV. The encapsulation efficiencies of TMZ and IR820 were 6.1 and 16.6%, respectively. Temperature increase curves under NIR laser irradiation indicated that the IT‑CSTNPs exhibited the desired photothermal conversion efficiency. The in vitro drug release curves revealed a suitable release capability of IT‑CSTNP under physiological conditions, whereas NIR laser irradiation accelerated the drug release. Inverted fluorescence microscopy and flow cytometry results revealed that the uptake of IT‑CSTNPs by A375 melanoma cells occurred in a concentration‑dependent manner. Confocal laser scanning microscopy results indicated that IT‑CSTNPs entered tumour cells via endocytosis and were located in intercellular lysosomes. In summary, the present study explored the photothermal conversion capability, cellular uptake, and intracellular localization of IT‑CSTNPs.

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