Uniform gold nanostars (Au NS) were conjugated with cyclic RGD (cRGD) and near infrared (NIR) fluorescence probe (MPA) or anti-cancer drug (DOX) to obtain multi-functional nanoconstructs, Au-cRGD-MPA and Au-cRGD-DOX respectively. The NIR contrast agent Au-cRGD-MPA was shown to have low cytotoxicity. Using tumor cells and tumor bearing mice, these imaging nanoparticles demonstrated favorable tumor-targeting capability mediated by RGD peptide binding to its over-expressed receptor on the tumor cells. The multi-therapeutic analogue, Au-cRGD-DOX, integrates targeting tumor, chemotherapy and photo-thermotherapy into a single system. The synergistic effect of photo-thermal therapy and chemotherapy was demonstrated in different tumor cell lines and in vivo using S180 tumor-bearing mouse models. The viability of MDA-MB-231 cells was only 40 % after incubation with Au-cRGD-DOX and irradiation with NIR light. Both tail vein and intratumoral injections showed Au-cRGD-DOX treated mice exhibiting the slowest tumor increase. These results indicate that the multifunctional nanoconstruct is a promising combined therapeutic agent for tumor-targeting treatment, with the potential to enhance the anti-cancer treatment outcomes.

Upconversion nanoparticles (UCNPs) have attracted much attention as potential photosensitizer carriers for photodynamic therapy (PDT) in deep tissues. In this study, hydrophilic UCNPs were prepared by coating amphiphilic chitosan (N-succinyl-N′-octyl chitosan, SOC) on the surface of hydrophobic oleic acid-capped NaYF₄ UCNPs (OA-UCNPs). Water-insoluble photosensitizer zinc(II) phthalocyanine (ZnPc) was loaded into the SOC-coated UCNPs (SOC-UCNPs) via hydrophobic interactions to form a novel drug delivery system for in vivo deep tissue PDT triggered by near-infrared (NIR) light. The ZnPc-loaded SOC-UCNPs exhibited good dispersibility, excellent optical properties and good photostability. Under NIR light irradiation, the measurement of singlet oxygen production indicated that ZnPc effectively generated singlet oxygen induced by the emission from the UCNPs. Cell viability assays showed the low cytotoxicity of the UCNPs after surface modification. In vitro and in vivo therapeutic investigation evidenced the prominent PDT effects of ZnPc-loaded SOC-UCNPs upon NIR light irradiation. Furthermore, NIR imaging of ICG derivative-loaded SOC-UCNPs after intra-tumoral injection indicated the high retention of SOC-UCNPs only in the tumor site. Histological examination confirmed the negligible toxicity of ZnPc-loaded SOC-UCNPs on other organs. All the results demonstrate the promising potential of using SOC-UCNPs as new photosensitizer carriers for PDT of cancer and other diseases in deep tissues.

The resistance of cancer cells to photothermal therapy is closely related to the overexpression of heat shock proteins (HSPs), which are abnormally upregulated when cells are under lethal stresses. Common strategies that use small molecule inhibitors against HSPs to enhance hyperthermia effect lack spatial and temporal control of drug release, leading to unavoidable systemic toxicity. Herein, a versatile photothermal platform is developed which is composed of a hollow gold nanoshell core densely packed with small interfering RNAs against heat shock protein 70 (Hsp70). Upon near infrared light irradiation, the small interfering RNAs can detach from gold surface specifically and escape from endosomes for Hsp70 silencing. Meanwhile, the temperature increases for hyperthermia therapy due to the high photothermal efficiency of the nanoshells. Efficient downregulation of Hsp70 after light activation is achieved in vitro and in vivo. Ultimately, the light‐controlled dual functional nanosystem, with the effects of Hsp70 silencing and temperature elevation, results in sensitized photothermal therapy in nude mice model under mild temperature. This strategy smartly combines the localized photothermal therapy with controlled Hsp70 silencing, and has great potential for clinical translation with a simple and easily controlled structure.