Smart Gold-Polymer Nanostructures As Promising Drug Nanocarriers For Dual-Imaging Modality And Synergistic Chemo-Photothermal Therapy in Breast Cancer Cells

To improve the efficacy of cancer therapeutics, highly sensitive imaging with precise accuracy is mandatory for timely diagnosis and selection of strategic approaches. Despite recent advances in technologies associated with tumor imaging, the application of conventional single-mode imaging is the subject of debate. Herein, two types of pH-responsive gold-polymer nanostructures, GNSts and GNRs, containing CD and MTX, GNSts-MTX@CD-Pol and GNRs-MTX@CD-Pol were designed. Dual-imaging modalities (fluorescence and CT imaging) and synergistic chemo-photothermal therapy were examined in human breast cancer MDA-MB 231 cells. MTT assay showed NIR irradiation of cells pre-treated with synthesized nanoparticles promoted tumoricidal synergy via the reduction of survival rate after 48 hours in comparison with the control group (p<0.05), indicating a high absorption coefficient in the NIR area and efficient heat production rate. Flow cytometry, real-time PCR and western blot, analyses indicated an apoptotic cell death induced by the up-regulation of Caspases 3, 6, 7, 8, and 9, Bax, and Annexin-V, confirming the activation of intrinsic and extrinsic apoptosis pathways inside the host cells. The elevation of p27 and p53 in line with the increase of cell percent at the subG1 phase showed apoptotic changes and inhibition of dynamic cell growth compared to the non-treated cells (p<0.05). Evident fluorescence intensity at lower pH values (6.3) showed pH-dependent activity of nanoparticles internalized by surface folate receptor. Of note, we showed strong capability for CT imaging in cells incubated with GNSts-MTX@CD-Pol and GNRs-MTX@CD-Pol. Taken together, all data show that gold-polymer nanostructures have considerable capability in theranostic applications like simultaneous diagnostic imaging and therapy.