Abstract
Photodynamic therapy (PDT) has been investigated as an effective, non-invasive, and alternative tumor-ablative therapy that uses photosensitizers (PSs) and safe irradiation light in the presence of oxygen to generate reactive oxygen species (ROS) to kill malignant cancer cells. However, the off-target activation of the PSs can hinder effective PDT. Therefore, an advanced drug delivery system is required to selectively deliver the PS to the therapeutic region only and reduce off-target side effects in cancer treatment. The integration of laser-initiated PDT with nanotechnology has provided new opportunities in cancer therapy. In this study, plasmonic bimetallic nanoparticles (NPs) were prepared for the targeted PDT (TPDT) of in vitro cultured MCF-7 breast cancer cells. The NPs were functionalized with PEG through Au–thiol linkage to enhance their biocompatibility and subsequently attached to the PS precursor 5-aminolevulinic acid via electrostatic interactions. In order to enhance specific targeting, anti-HER-2 antibodies (Ab) were decorated onto the surface of the nanoconjugate (NC) to fabricate a 5-ALA/Au–Ag-PEG-Ab NC. In vitro studies showed that the synthesized NC can enter MCF-7 cells and localize in the cytoplasm to metabolize 5-ALA to protoporphyrin IX (PpIX). Upon light irradiation, PpIX can efficiently produce ROS for the PDT treatment of MCF-7. Cellular viability studies showed a decrease from 49.8% ± 5.6 ** to 13.8% ± 2.0 *** for free 5-ALA versus the NC, respectively, under equivalent concentrations of the PS (0.5 mM, IC50). These results suggest that the active targeted NC platform has an improved PDT effect on MCF-7 breast cancer cells.
Highlights
Breast cancer is the most common malignancy in women and affects approximately one-eighth of women worldwide [1]
photodynamic therapy (PDT) is a minimally invasive cancer therapeutic modality that is based on the administration of a photosensitizer (PS) to cancer tissues followed by irradiation, at an appropriate wavelength of light, to excite the PSs to produce reactive oxygen species (ROS) to obliterate neoplastic tissue [3]
The high stability of the synthesized bimetallic citrate Au–Ag NPs was repulsions between NPs and so no aggregation was observed [39]. This finding was condue to the presence of sodium citrate, which induces an abundance of negative charges, firmed by UV-Visible spectroscopy and the reported polydispersity indexes (PDIs)
Summary
Breast cancer is the most common malignancy in women and affects approximately one-eighth of women worldwide [1]. Some promising therapeutic modalities, such as chemotherapy, radiotherapy, and surgery, have been developed, the major setback is still associated with traditional techniques, whereby they affect healthy cells and induce major side effects [2]. Laser-induced photodynamic therapy (PDT) together with photosensitizer (PS) delivery has emerged to overcome the limitations of conventional therapies and obliterate cancer cells. PDT is a minimally invasive cancer therapeutic modality that is based on the administration of a photosensitizer (PS) to cancer tissues followed by irradiation, at an appropriate wavelength of light, to excite the PSs to produce reactive oxygen species (ROS) to obliterate neoplastic tissue [3]. PDT provides minimal side effects, low morbidity, and good tolerance [3].
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