SERS imaging elucidates the folate receptor-mediated photothermal/photodynamic synergistic anticancer nanodrugs-induced cell apoptosis

Abstract Background: Chemotherapy and radiotherapy are common methods of cancer treatment, but they are accompanied by serious side effects. Actually, many cancer cells have overexpression of folic acid (FA) receptor and by FA receptor-mediated endocytosis, anticancer drugs can be easily internalized into cancer cell, this will greatly improve the curative effect and decrease side effects. Along with the development of nanotechnology, phototherapy, owning advantages in tissue selectivity, process controlling, low toxicity and reproducible treatment, has become very promising, especially for photothermal therapy (PTT) and photodynamic therapy (PDT). Since both PTT and PDT involve the utilization of light energy, so they synergistic treatment should be a good solution by ingenious design. In this paper, based on surface enhanced Raman spectroscopy (SERS) imaging, we hope to construct a FA receptor-mediated PTT/PDT synergistic anticancer nanodrug (nanoprobe), and achieve the intracellular distribution information of the nanodrugs during cell apoptosis, and then elucidate PTT/PDT-induced cell apoptosis and synergistic efficiency.Results: FA receptor-mediated PTT/PDT synergistic anticancer nanodrugs with tracing function are prepared by the chemical synthesis and modification of gold nanorods (GNR), involving protoporphyrin IX (PpIX), 4-mecaptobenzoic acid (MBA), and FA. Based on SERS imaging, it is found that the FA receptor-mediated endocytosis can greatly facilitate the nanodrugs internalization, in which both the number and intracellular dispersion of the PpIX-GNR-MBA-FA nanodrugs are improved relative to the GNR-MBA or PpIX-GNR-MBA compositions, and then enhance the PTT/PDT-induced cell apoptosis.Conclusion: SERS imaging is very suitable for the phototherapy tracing due to its high sensitivity and stability. The FA receptor-mediated way can significantly facilitate nanodrugs internalization, PTT/PDT-induced cell apoptosis and synergistic efficiency. Importantly, this FA receptor-mediated SERS imaging based PTT/PDT synergistic treatment will provide a novel strategy for the design and application of anticancer phototherapy nanodrugs.