Combined Chemo‐Photothermotherapy Using Gold Nanoshells on Drug‐Loaded Micellar Templates for Colorectal Cancer Treatment

Combined chemo‐photothermotherapy is a novel strategy to improve the therapeutic outcome of cancer treatment by the synergistic effects of both photothermal therapy (PTT) and chemotherapy. Here, multifunctional gold nanoshells (GNS) that are synthesized using the 7‐ethyl‐10‐hydroxycamptothecin (SN‐38)‐loaded micellar template are presented. The surface of positively charged SN‐38‐encapsulated poly[2‐(N,N‐dimethylamino)ethyl methacrylate]–poly(ε‐caprolactone) (PDMA–PCL) micelles is decorated with a gold layer by in situ reduction of chloroauric acid (HAuCl4). The GNS display a broad surface plasmon resonance peak in the near‐infrared (NIR) wavelength region and high photothermal conversion ability. After PEGylation, the GNS are stable in biological media and appear highly biocompatible. Upon NIR laser irradiation, the PEGylated gold nanoshells on SN‐38‐encapsulated micelles (SN‐38@pGNS) convert incident energy to heat, which causes local temperature increase and facilitates the release of the encapsulated drug. Combined chemo‐photothermotherapy using SN‐38@pGNS with laser irradiation kills colorectal cancer cells with higher efficacy in vitro and demonstrates significant tumor suppression in vivo compared to using single therapy such as chemotherapy or PTT alone. This suggests that GNS on drug‐loaded micelles deliver SN‐38 and PTT synergistically and may be a potential candidate for future colorectal cancer therapy. Combined chemo‐photothermotherapy is a novel strategy to improve the therapeutic outcome of cancer treatment. The poly[2‐(N,N‐dimethylamino)ethyl methacrylate]–poly(ε‐caprolactone) micellar templates are employed to create gold nanoshells that not only act as a drug delivery system but also provide a remarkable photothermotherapy effect. With the delivered drug and photothermotherapy working synergistically, gold nanoshells with the dual therapeutic effect significantly suppress the tumor growth.