Despite advances in controlled
drug delivery, reliable methods for activatable, high-resolution control of drug release are needed. The hypothesis that the photothermal effect mediated by a near-infrared (NIR)
laser and hollow
gold nanospheres (HAuNSs) could modulate the release of
anticancer agents is tested with biodegradable and biocompatible
microspheres (1-15 microm) containing the
antitumor drug paclitaxel (PTX) and HAuNSs (approximately 35 nm in diameter), which display surface plasmon absorbance in the NIR region. HAuNS-containing
microspheres exhibit a NIR-induced thermal effect similar to that of plain HAuNSs. Rapid, repetitive PTX release from the PTX/HAuNS-containing
microspheres is observed upon irradiation with NIR light (808 nm), whereas PTX release is insignificant when the NIR light is switched off. The release of PTX from the
microspheres is readily controlled by the output power of the NIR
laser, duration of irradiation, treatment frequency, and concentration of HAuNSs embedded inside the
microspheres. In vitro,
cancer cells incubated with PTX/HAuNS-loaded
microspheres and irradiated with NIR light display significantly greater cytotoxic effects than cells incubated with the
microspheres alone or cells irradiated with NIR light alone, owing to NIR-light-triggered drug release. Treatment of human U87
gliomas and MDA-MB-231 mammary
tumor xenografts in nude mice with intratumoral
injections of PTX/HAuNS-loaded
microspheres followed by NIR irradiation results in significant
tumor-growth delay compared to
tumors treated with HAuNS-loaded
microspheres (no PTX) and NIR irradiation or with PTX/HAuNS-loaded
microspheres alone. The data support the feasibility of a therapeutic approach in which NIR light is used for simultaneous modulation of drug release and induction of photothermal cell killing.