A pH-Driven and photoresponsive nanocarrier: Remotely-controlled by near-infrared light for stepwise antitumor treatment

Abstract The hollow gold nanospheres (HAuNS) have shown medicinal promise due to their inert and nontoxic properties with unique photothermal therapy capabilities. In this study, the electrostatic approach was employed to successfully absorb Chlorin e6 (Ce6) simultaneously with the pH (low) insertion peptide (pHLIP) onto surface of HAuNS, forming HAuNS-pHLIP-Ce6 with desirable pH-driven and NIR light-stimulated controlled therapeutical effect. The HAuNS-pHLIP-Ce6 experienced hyperthermia within 5 min of laser exposure, which marked the photothermal therapy (PTT) and deduced the agents release due to the reduction of electrostatic interaction. The improved strategy facilitated a stepwise photoresponsive system capable of active accumulation and retention effects, photothermal ablation of tumor cells, release of photosensitizers (PS), and subsequently photodynamic therapy (PDT) in a single light irradiation session. The smart delivery system had been proved with multi-functionalities via conjugated targeting ligand and PS. The external absorption of patient tailored medication combinations was also possible with this treatment platform.