Enhanced Cytotoxic Effect of TAT–PLGA-Embedded DOXO Carried by Biomimetic Magnetic Nanoparticles upon Combination with Magnetic Hyperthermia and Photothermia

Pharmaceutics

Guillermo R. Iglesias¹  María P. Carrasco-Jiménez²  Alberto Sola-Leyva²  Massimiliano Perduca³  Salvatore Calogero Gaglio³  Concepcion Jimenez-Lopez⁴  Ylenia Jabalera⁴ 

[1] Department of Applied Physic, Faculty of Sciences, University of Granada, 18071 Granada, Spain;Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain;Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona, Italy;Department of Microbiology, Faculty of Sciences, University of Granada, 18071 Granada, Spain;

关键词: photothermia;    hyperthermia;    BMNPs;    PLGA;    magnetic nanoparticles;    TAT peptide;   

DOI  :  10.3390/pharmaceutics13081168

来源: DOAJ

【 摘 要 】

The synergy between directed chemotherapy and thermal therapy (both magnetic hyperthermia and photothermia) mediated by a nanoassembly composed of functionalized biomimetic magnetic nanoparticles (BMNPs) with the chemotherapeutic drug doxorubicin (DOXO) covered by the polymer poly(lactic-co-glycolic acid) (PLGA), decorated with TAT peptide (here referred to as TAT–PLGA(DOXO-BMNPs)) is explored in the present study. The rationale behind this nanoassembly lies in an optimization of the nanoformulation DOXO-BMNPs, already demonstrated to be more efficient against tumor cells, both in vitro and in vivo, than systemic traditional therapies. By embedding DOXO-BMNPs into PLGA, which is further functionalized with the cell-penetrating TAT peptide, the resulting nanoassembly is able to mediate drug transport (using DOXO as a drug model) and behaves as a hyperthermic agent (induced by an alternating magnetic field (AMF) or by laser irradiation with a laser power density of 2 W/cm²). Our results obtained using the HepG2 cell line show that there is a synergy between chemotherapy and thermal therapy that results in a stronger cytotoxic effect when compared to that caused by the soluble DOXO. This is probably due to the enhanced DOXO release occurring upon the application of the thermal therapy, as well as the induced local temperature rise mediated by BMNPs in the nanoassembly following exposition to AMF or to near-infrared (NIR) laser irradiation. These results represent a proof of concept demonstrating that TAT–PLGA(DOXO-BMNPs) can be used to efficiently combine therapies against tumor cells, which is a step forward in the transition from systemic to local treatments.

【 授权许可】

Unknown