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Dissolving microneedles integrated with pH-responsive micelles containing AIEgen with ultra-photostability for enhancing melanoma photothermal therapy.
Biomaterials Science 2020 September 19
Photothermal therapy (PTT) based on aggregation-induced emission luminogen (AIEgen) is very promising for superficial tumor therapy due to the superior photostability and photothermal conversion efficiency of AIEgens. However, the systemic administration of AIEgen remains challenging, mainly because of solubility dissatisfaction and biodistribution. Here, a dissolving microneedle (MN) system loaded with AIEgen (NIR950) was developed for topical administration to treat malignant skin tumor melanoma. Firstly, NIR950-loaded polymeric micelles (NIR950@PMs) were prepared via a nanoprecipitation method to increase the drug solubility. Then, micelles were concentrated on needle tips of MN (NIR950@PMs@MN) by a two-step molding method. NIR950@PMs showed no distinct decline in emission intensity under continuous laser irradiation for an hour. Moreover, the pH-responsive micelles can be protonated in an acidic tumor microenvironment to facilitate the intracellular uptake. By virtue of dissolving MN, NIR950@PMs could rapidly accumulate at the tumor site and reach a suitable temperature for killing cancer cells under laser irradiation. With only single administration and one-time laser irradiation, the NIR950@PMs@MN could notably eliminate melanoma tumors with a low dose of NIR950. Overall, this dissolving MN system loaded with NIR950 showed remarkable photostability and also achieved a valid photothermal effect, which indicate great potential for clinical superficial tumor therapy.
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