Degradable NIR-PTT Nanoagents with a Potential Cu@Cu₂O@Polymer Structure

Cu@Cu₂O@PSMA polymer nanoparticles (Cu@Cu₂O@polymer NPs) with near-infrared (NIR) absorption were successfully synthesized in a single-step oxidation reaction of Cu@PSMA polymer NPs at 100 °C for 20 min. The shape, structure, and optical properties of the Cu@Cu₂O@polymer NPs were tailorable by controlling the reaction parameters, for example, using the initial Cu@PSMA polymer NP as a template and varying the halide ion content, heating temperature, and reaction time. The Cu@Cu₂O@polymer NPs exhibited robust NIR absorption between 650 and 710 nm and possessed superior oxidation resistance in water and culture media. In vitro assays demonstrated the low cytotoxicity of the Cu@Cu₂O@PSMA polymer NPs to HeLa cells through an improved cell viability, high IC₅₀, low injury incidence from the supernatant of the partly dissociated Cu@Cu₂O@PSMA polymer NPs, and minor generation of reactive oxygen species. More importantly, we demonstrated that the inorganic Cu-based nanocomposite [+0.34 V vs normal hydrogen electrode (NHE)] was degradable in an endogenous H₂O₂ (+1.78 V vs NHE) environment. Cu ions were detected in the urine of mice, which illustrates the possibility of extraction after the degradation of the Cu-based particles. 'After an treatment of the HeLa cells with the Cu@Cu₂O@polymer NPs and a 660 nm light-emitting diode, the photoablation of 50 and 90% cells was observed at NP doses of 20 and 50 ppm, respectively. These results demonstrate that NIR-functional and moderate redox-active Cu@Cu₂O@polymer NPs are potential next-generation photothermal therapy (PTT) nanoagents because of combined features of degradation resistance in the physiological environment, enabling the delivery of efficient PTT, a possibly improved ability to selectively harm cancer cells by releasing Cu ions under high-H₂O₂ and/or low-pH conditions, and ability to be extracted from the body after biodegradation.