Improving chemoradiotherapy strategy with PEGylated doxorubicin loaded gold nanoparticles against oral cancers

Abstract

Chemoradiotherapy, a combination treatment paradigm in oncology, where chemotherapy and radiation therapy are administered concurrently. Nanomedicine based Drug delivery at tumour site and radiosensitizer can minimize the adverse effects of chemoradiation. In this study, one pot and facile method was used to synthesize two nanotherapeutics Doxorubicin reduced gold nanoparticles (Au Dox NPs) and Doxorubicin complexed in PEGylated gold nanoparticles (Au Dox PEG NPs). Both were physico-chemically characterized by spectroscopy methods to confirm formation of gold nanoparticles and conjugation of Dox. Advanced electron microscopy was used to analyze morphology and nano architect of the nanotherapeutics. Drug release kinetics was analyzed by dialysis method. KB cells were X-ray irradiated by LINAC facility at 4 Gy dose. Cytotoxicity, radiation and chemoradiation damage was measured by MTT assay. Stability assay to measure the agglomeration and stability in biological medium. The resultant two nanotherapeutics synthesized, Au Dox NPs and Au Dox PEG NPs are stable nanoformulations successfully loaded with Dox. Both had average size of ∼20 nm and negative surface charge and near spherical morphology. Conjugated Dox molecule is conserved. KB cancer cell line in vitro cellular studies revealed that the Au Dox NPs had enhanced drug uptake and superior cytotoxicity and radiosensitization in comparison to Au Dox PEG NPs and free Dox, thereby providing a synergistic approach for treatment of oral cancer. In the current study promising results obtained at preclinical in vitro model, the potential of Au Dox PEG NPs for drug delivery system can be enhanced by tagging with antibodies/small molecules for targeted treatment of oral cancers, also further investigation in vivo model warranted.