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Flav7 + DOX co-loaded separable microneedle for light-triggered chemo-thermal therapy of superficial tumors

Huixin Wang,Wenshen Wang,Chengpan Li,Ao Xu,Bensheng Qiu,Fenfen Li,Weiping Ding

Microneedles (MNs) are an attractive strategy for the efficient, painless transdermal delivery of drugs with low systemic toxicity. In this work, a novel near-infrared (NIR) light-triggered separable microneedle system was fabricated to supply controlled chemo-thermal therapy to superficial tumors by co-loading a self-developed NIR-II fluorescence fluorophore Flav7 and the antitumor drug doxorubicin (DOX) in phase-change polycaprolactone (PCL) arrowheads on a soluble base. For the MNs we proposed, Flav7 offers MNs with NIR light-triggered heating generation and drug release properties as well as a NIR-II imaging ability for guiding combined chemo-thermal therapy, and the soluble supporting base ensures that the needle arrows are embedded in the skin after insertion and endows the MNs with a separation ability to reduce the contact time of the MNs with the skin. In vitro studies showed that Flav7 + DOX-loaded MNs exhibited adequate insertion abilities, stable thermal properties, and desirable light-activated melting effects and drug release capabilities. In vivo studies showed that the Flav7 + DOX-loaded MNs presented a remarkable NIR-II imaging ability, a good biosafety to the major organs, and a strong tumor-killing ability. It is worth noting that all of the treated breast cancer mice survived for 50 days without tumor recurrences or major organ damage. This study presented a promising MN system loaded with the multipurpose small molecule Flav7 that can be used for high-efficiency light-activated drug release for chemotherapy and high-performance light-controlled thermotherapy of tumors and also for remarkable NIR-II fluorescence imaging to guide chemo-thermal therapy.