A Dual-Color Luminescent Localized Drug Delivery System with Ratiometric-Monitored Doxorubicin Release...

Implantable localized drug delivery systems (LDDSs) have been intensively investigated for cancer therapy. However, the anticancer agent release behavior as well as the local therapeutic process in the complex physiological environment remains a dark zone and consequently hinders their clinical applications. Herein, a series of Er³⁺-doped electrospun strontium titanate (SrTiO₃, STO) nanofibers with refined microstructural characteristics were exploited as a localized carrier for doxorubicin (DOX) delivery due to its light-responsive functionalities as well as expected biocompatibility. The highest DOX loading capacity and sustained releasing kinetics were obtained from the nanofibers with the highest surface area and lowest pore dimensions. Consequently, such nanofibers presented stronger in vitro anticancer efficacy to Hep G2 cells compared to that of other samples. More importantly, the amount of drug released was monitored by the ratio of green-to-red emission (I₅₅₀/I₆₆₀) due to the fluorescence resonance energy transfer (FRET) effect built between DOX molecules and upconversion photoluminescent nanofibers. The selective quenching effect of green emission due to DOX molecules was gradually weakened with drug releasing progress, whereas the intensity of red emission barely changed, resulting in an increased I₅₅₀/I₆₆₀ ratio. Such color evolution can be feasibly visualized by the naked eye. Monitoring with a spectral intensity ratio eliminates the disturbance of uncertainties in the complex physiological environment compared to just referring to the emission intensity. Such dual-color luminescent STO:Er nanofibers, designed based on the FRET mechanism, are therefore considered to be a promising new LDDS platform with ratiometric-monitored DOX release functionalities for future localized tumor therapeutic strategies.