4.8 Article

Dual targeting smart drug delivery system for multimodal synergistic combination cancer therapy with re duce d cardiotoxicity

Journal

ACTA BIOMATERIALIA
Volume 131, Issue -, Pages 493-507

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2021.06.016

Keywords

Magnetic photothermal nanoparticles; Cardiotoxicity; Smart drug delivery system; Dual targeting; Cancer; Chemo-photothermal-starvation combination therapy

Funding

  1. Ministry of Science and Technology [EAS-429]

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This study describes the development of a smart drug delivery system for multimodal synergistic cancer therapy, utilizing chemo-photothermal-starvation approaches to improve drug release and cellular uptake as well as achieve a synergistic therapeutic effect for cancer treatment.
This study first reports the development of a smart drug delivery system (DDS) for multimodal synergistic cancer therapy combining chemo-photothermal-starvation approaches. A magnetic photothermal agent was synthesized by preparing iron oxide (IO) nanoparticles (NPs) with covalently attached indocyanine green (ICG) and glucose oxidase (GOx) (ICGOx@IO). Synthesized ICGOx@IO NPs were coencapsulated with doxorubicin (Dox) and EGCG ((-)-epigallocatechin-3-gallate) inside PLGA (poly(lacticco-glycolic acid)) NPs using multiple emulsion solvent evaporation method. Such formulation gave the advantage of triggered drug release by near-infrared (NIR) laser irradiation (808 nm at 1 W/cm 2 ). RGD peptide was attached to the surface of PLGA NPs and the final hydrodynamic size was around 210 nm. Dual targeting by peptide and 240 mT external magnet significantly improved cellular uptake. Cellular uptake was observed using FACS, electron and optical microscopy. Dual targeting along with laser irradiation could reduce in vitro cell viability by 90 +/- 2% (Dox-equivalent dose: 10 mu g/ml) and complete tumor ablation was achieved in vivo due to synergetic therapeutic effect. Another attractive feature of the DDS was the significant reduction of cardiotoxicity of doxorubicin by EGCG. This new platform is thus expected to hold strong promise for future multimodal combination therapy of cancers.

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