Targeted Combinatorial Therapy Using Gold Nanostars as Theranostic Platforms

Abstract

This paper reports the development of a multimodal therapy nanoplatform based on gold nanostars (Au NS) as core particles. These NS were functionalized with the chemotherapeutic drug doxorubicin (DOXO), which was conjugated to the NS surface by means of a cleavable heterobifunctional cross-linker (sulfo-LC-SPDP) to allow its release under the action of reducing enzymes. To ensure a specific delivery of the chemotherapeutic drug, the nanoplatform was additionally functionalized with folic acid (FA) as targeting ligand and cellular uptake adjuvant. By synthetically modifying the plasmon band of Au NS to the near-infrared (NIR) region of the electromagnetic spectrum, the present nanoplatform was able to simultaneously combine the capability of photothermal therapy (PTT) through the conversion of absorbed light energy into localized heat and chemotherapy, enabling their monitoring by means of optical fluorescence imaging thanks to DOXO’s autofluorescence. Cellular uptake was observed to be enhanced when the Au NPs were decorated with the targeting ligand. In addition, the therapeutic efficiency of the nanoplatform tested in HeLa cells demonstrated the larger cytotoxicity efficiency of the combined therapy if compared to individual ones.