Fu Yike, Chen Xiaoyi, Mou Xiaozhou, Ren Zhaohui, Li Xiang, Han Gaorong
State Key Laboratory of Silicon Materials, School of Materials Science and Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, P. R. China.
Clinical Research Institute, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, P. R. China.
ACS Biomater Sci Eng. 2016 Apr 11;2(4):652-661. doi: 10.1021/acsbiomaterials.6b00046. Epub 2016 Mar 30.
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 Er-doped electrospun strontium titanate (SrTiO, 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 (/) 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 / 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.
可植入局部给药系统（LDDSs）已被深入研究用于癌症治疗。然而，在复杂生理环境中的抗癌药物释放行为以及局部治疗过程仍然是一个未知领域，因此阻碍了它们的临床应用。在此，一系列具有精细微观结构特征的掺铒电纺钛酸锶（SrTiO₃，STO）纳米纤维因其光响应功能以及预期的生物相容性而被开发用作阿霉素（DOX）递送的局部载体。具有最高表面积和最小孔径的纳米纤维获得了最高的DOX负载量和持续释放动力学。因此，与其他样品相比，此类纳米纤维对Hep G2细胞表现出更强的体外抗癌功效。更重要的是，由于DOX分子与上转换光致发光纳米纤维之间建立的荧光共振能量转移（FRET）效应，通过绿色与红色发射的比率（I₅₂₀/I₆₅₀）来监测药物释放量。随着药物释放过程，DOX分子对绿色发射的选择性猝灭效应逐渐减弱，而红色发射强度几乎不变，导致I₅₂₀/I₆₅₀比率增加。这种颜色变化可以用肉眼轻松观察到。与仅参考发射强度相比，用光谱强度比率进行监测消除了复杂生理环境中不确定性的干扰。因此，基于FRET机制设计的这种双色发光STO:Er纳米纤维被认为是一种有前途的新型LDDS平台，具有用于未来局部肿瘤治疗策略的比率监测DOX释放功能。
