Effect of TAT-PLGA - DOx transported by biomimetic magnetic nanoparticles under magnetic hyperthermia and photothermia irradiation

The study delves into the synergistic potential of combining targeted chemotherapy with thermal therapy, encompassing magnetic hyperthermia and photothermia. This amalgamation is facilitated by a nanoassembly comprising specialized biomimetic magnetic nanoparticles (BMNPs) laden with the potent chemotherapeutic agent doxorubicin (DOXO), ensconced within a polymeric shell of poly(lactic-co-glycolic acid) (PLGA) and adorned with TAT peptide (termed TAT–PLGA(DOXO-BMNPs)). Notably, prior studies have utilized PLGA to encapsulate both MNPs [1] and BMNPs [2]. In a recent investigation, we demonstrated that the incorporation of PLGA and/or TAT–PLGA coating onto BMNPs enhances cellular uptake without compromising the magnetic properties critical for hyperthermic functionality. However, the potential synergy between directed chemotherapy and magnetic hyperthermia remained unexplored in that study, owing to the lack of BMNP functionalization. Additionally, the capability of TAT–PLGA-embedded DOXO-BMNPs to facilitate synergy between chemotherapy and photothermia, as an innovative means to elevate local temperatures and/or promote drug release at the tumor site, has yet to be investigated. Our findings with the HepG2 cell line demonstrate a compelling synergistic effect between chemotherapy and thermal therapy, resulting in heightened cytotoxicity compared to soluble DOXO alone. This augmentation is ascribed to the enhanced release of DOXO facilitated by thermal therapy, coupled with the localized temperature elevation induced by BMNPs within the nanoassembly upon exposure to AMF or NIR laser irradiation. These results underscore the potential of TAT–PLGA(DOXO-BMNPs) as a versatile platform for combining therapies against tumor cells, representing a pivotal step toward transitioning from systemic to localized treatments. This innovation holds promise for more efficacious and precisely targeted cancer therapies. Therefore, in the present study, our aim was to optimize the effectiveness of the DOXO-BMNP nanoassembly, utilizing DOXO as a model drug molecule, through various approaches. Specifically, we sought to enhance cellular uptake by embedding DOXO-BMNPs within TAT peptide-functionalized PLGA nanoparticles while concurrently combining this optimized directed chemotherapy with magnetic hyperthermia and photothermia