Cancer Cell-Specific Enhanced Raman Imaging and Photothermal Therapeutic Effect Based on Reversibly pH-Responsive Gold Nanoparticles.

Abstract

Stimuli-responsive nanoparticles are favorable for improving the selective delivery and rational vocation that easily avoids the undesirable barriers or side effects, leading to a further improved therapeutic efficiency. Furthermore, multifunctional nanomaterials have been extensively developed as attractive candidates for theranostic reagents for cancer treatment. In this article, we developed reversibly pH-responsive gold nanoparticles (AuNPs) with an enhanced Raman scattering signal as well as an efficient photothermal effect and demonstrated their applications as a theranostic reagent for cancer treatment. Surfaces of these AuNPs were modified with mixed layers of Cy3-modified single-stranded DNA (ssDNA-Cy3) for Raman probing and a negative charge supply and cytochrome C (Cyt C) for pH-responsive charge inversion. This combination of pH-responsive ligands and Raman probes played an important role in inducing the assembly or disassembly of AuNPs corresponding to the neighboring pH, accompanied by an additional highly distinguished Raman signal intensity. An operative reversible response of the AuNPs to pH is endowed with the characteristic behavior of AuNPs with the cancerous cell's acidic microenvironment of low pH. The responsive aggregation of AuNPs in a lower pH medium provides highly amplified signals attributed to well-formed hot spots between the particle surfaces that deliver better Raman scattering signals. The acidic pH-responsive aggregation of the particles also provided efficient photothermal treatments using a long-wavelength laser light with the benefit of deeper penetration for cancer cells. In vitro experiments employing cancer cells and control normal cells well-demonstrated the specificity of the particles to cancer cells in terms of highly enhanced Raman imaging and therapeutic efficiency.