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

Abstract

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.