Reactive oxygen species and near-infrared light dual-responsive indocyanine green-loaded nanohybrids for overcoming tumour multidrug resistance

Abstract The nucleus is in charge of the metabolism and heredity of the cell, and genetic mutations are closely related with tumour multidrug resistance (MDR). Indocyanine green (ICG), the FDA-approved photosensitizer, is widely used for tumour photodynamic therapy (PDT) and photothermal therapy (PTT). Few studies have clarified the cellular distribution of ICG in MDR tumour cells. In the study, ICG distribution was detected in the whole tumour cells of MCF-7 and MCF-7/ADR, especially in the nucleus, which led us to question whether increasing cellular accumulation and nuclear distribution of ICG could be a potential method to overcome MDR. Therefore, a reactive oxygen species (ROS) and near-infrared (NIR) light dual-responsive nanohybrid was constructed with diselenide cross-linked polyamidoamine-Poloxamer 188 and graphene oxide with ICG as payloads (ICG/GPP). The nanohybrid enhanced the stability of ICG and showed an ROS-sensitive release behaviour. More ICG was delivered by ICG/GPP to the MCF-7/ADR cells. After escaping from the lysosome, nuclear accumulation of ICG was increased. Under NIR laser irradiation, ICG/GPP showed increased cytotoxicity for the combined PTT and PDT in MCF-7/ADR cells. Moreover, the expression of P-glycoprotein (P-gp) was suppressed to overcome tumour MDR. The ROS- and NIR- responsive GPP shows potential for the nuclear delivery of drugs to combat tumour MDR.