Abstract
The present study developed a novel multifunctional nanoparticle capable of being targeted passively to the tumor site, mediating sustained drug release as well as providing photothermal therapy. This fabricated nanoparticle is mesoporous silica-loaded doxorubicin covered with a thin layer of pegylated gold (PEG-DOX-MPS-GNSs). The prepared nanoparticles were characterized using transmission electron microscopy, energy dispersive X-ray analysis, UV-VIS absorption spectroscopy, dynamic light scattering, zeta potential measurements and small angle X-ray diffraction. The prepared mesoporous silica nanopartides (MPS) were approximately 150 nm in diameter and were characterized by its well-ordered mesoporosity of d-spacing similar to 4.5 nm, which enabled a high doxorubicin-loading capacity. Laser scanning confocal microscopy was used to study the dynamics and cellular uptake of PEG-DOX-MPS-GNSs, in addition to its therapeutic efficiency upon NIR irradiation. Superior cytotoxicity in MCF-7 cells was obtained for irradiated PEG-DOX-MPS-GNSs compared with other experimental groups. Intravenous application of PEG-DOX-MPS-GNSs (1 mg/kg), followed by NIR irradiation of the tumor area, inhibited the growth of subcutaneous Ehrlich carcinoma in vivo (p < 0.0001) and induced a stronger anticancer effect compared to other applied oncological modalities. Moreover, histopathological examination demonstrated a high percentage of necrosis in PEG-DOX-MPS-GNSs-treated group (97%) compared with NIR (34%) or control (18%) groups, which was consistent with the in vitro and in vivo findings. Thus, in this context, we present a novel strategy for preparing a photothermal responsive formulation (PEG-DOX-MPS-GNSs), demonstrating the controlled DOX-release behavior and its therapeutic effect. These prepared multifunctional nanoparticles can efficiently convert laser energy into heat, which in turn induces thermal damage and delivery of doxorubicin to the tumor site with a subsequent high therapeutic efficacy. (C) 2014 Elsevier Inc. All rights reserved.