Large payloads of gold nanoparticles into the polyamine network core of stimuli-responsive PEGylated nanogels for selective and noninvasive cancer photothermal therapy

A biocompatible photothermal nanomedicine based on a PEGylated nanogel containing gold nanoparticles (GNPs) in a cross-linked network core of stimuli-responsive poly[2-(N,N-diethylamino)ethyl methacrylate] (PEAMA) gel for cancer photothermal therapy (PTT) was prepared through the reduction of Au(iii) ions without any reducing agents. The influence of the reduction conditions, such as pH, temperature, and N/Au ratio (molar ratio of the amino groups in the PEGylated nanogel to the Au(iii) ions), on the formation of the GNPs in the stimuli-responsive PEAMA gel core (reducing environment) was also studied. Note that the PEGylated nanogel containing GNPs prepared at pH 6, 60 °C and N/Au = 1 (PEGylated GNG (1)) was found to have the highest GNP-loading capacity with a diameter of about 8 nm, as observed by TEM; viz., about 27 GNPs formed in a single PEAMA gel core. PEGylated GNG (1) showed a remarkable photothermal efficacy (ΔT = 7.7 °C) under irradiation with Ar ion (Ar⁺) laser (514.5 nm) at a fluence of 39 W cm^-2 for 6 min (14 kJ cm ^-2). Note that PEGylated GNG (1) showed non-cytotoxicity in the absence of irradiation with Ar⁺ laser (480 μg mL^-1: > 90% cell viability), whereas pronounced cytotoxicity (IC₅₀ = 110 μg mL^-1) was observed for PEGylated GNG (1) under irradiation with Ar⁺ laser at a fluence of 26 W cm^-2 for 5 min (7.8 kJ cm^-2), because of the heat-generation from the GNPs in the cells, which resulted in selective and noninvasive cancer PTT. Thus, PEGylated GNG (1), which has a high GNP-loading capacity, would be a promising nanomedicine for cancer PTT.