Thermosensitive nanogel-based oxaliplatin delivery system for synergistic intratumoral radiofrequency chemotherapy

To achieve sustained release and prolonged tumor retention of oxaliplatin (OXA), a thermosensitive OXA-loaded poly(N-isopropyl acrylamide-co-acrylic acid) nanogel (PAAs) was developed via a synergistic mixing-stirring method. The formulation, consisting of 0.8 mg/mL OXA thoroughly dispersed in 8% poly(N-isopropyl acrylamide-co-acrylic acid) nanogel (PNAs), exhibited favorable radiofrequency responsiveness, thermosensitivity, and controlled-release properties, enabling continuous OXA release for up to five days. The sol-gel phase transition behavior of the thermosensitive PAAs nanogel was characterized using the vial-inversion method and rheological analysis. Platinum content analysis revealed enhanced tumor retention of the PAAs nanogel compared with free OXA, as evidenced by significantly higher platinum levels in tumors treated with the nanogel formulation. In vivo antitumor efficacy evaluation demonstrated that a single administration of the PAAs nanogel resulted in sustained tumor regression, reducing the relative tumor volume to 0.81 ± 0.06 times the initial volume within 14 days. In contrast, treatment with an equivalent dose of free OXA, PNAs alone, or normal saline led to rapid tumor progression, with tumor volumes increasing to 3.22 ± 0.65, 7.01 ± 0.47, and 10.07 ± 1.57 times the initial volume, respectively. Preliminary biocompatibility assessment indicated that the incorporation of OXA into PNAs within the nanogel significantly alleviated the toxic side effects associated with free OXA. These findings underscore the considerable potential of the PAAs nanogel as a versatile strategy to enhance the antitumor efficacy of platinum-based drugs while mitigating their systemic toxicity and size-related limitations. This system therefore represents a promising candidate for further development as a novel nanomedicine for localized chemotherapy.