■目前,已经报道的少数关于视网膜母细胞瘤的光热/化疗研究主要限于涉及皮下植入的异位模型.然而,眼球是独特的生理结构,血-视网膜屏障(BRB)阻碍药物分子通过全身途径的吸收。此外,眼底丰富的血液循环加速药物代谢。为了维持所需的药物浓度,患者必须进行频繁的化疗.
■为了应对上述挑战,我们需要开发一种安全有效的眼底给药系统(FA-PEG-PDA-DOX)。
■我们提供了卓越的治疗功效,副作用最小或没有副作用,并成功建立了原位小鼠模型。我们评估了FA-PEG-PDA-DOX纳米系统的细胞摄取性能和靶向效率,并评估了其在体外和体内的协同抗肿瘤作用。进行生物分布评估以确定NPs在体内的保留时间和靶向效率。此外,进行了安全性评估。
■FA-PEG-PDA-DOX激光组的细胞内吞率为DOX组的5.23倍,是FA-PEG-PDA-DOX组的2.28倍。FA-PEG-PDA-DOX的荧光信号在肿瘤部位持续超过120小时。光热化疗组增殖周期内肿瘤细胞数量(17.2%)减少61.6%,与生理盐水对照组(78.8%)相反。FA-PEG-PDA-DOX纳米颗粒(NPs)具有良好的生物安全性和高生物相容性。
■双功能靶向纳米系统,在DOX和辐射温和升温的影响下,在裸鼠模型中产生精确的化学/光热疗法。
UNASSIGNED: At present, the few photothermal/chemotherapy studies about retinoblastoma that have been reported are mainly restricted to ectopic models involving subcutaneous implantation. However, eyeball is unique physiological structure, the blood-retina barrier (BRB) hinders the absorption of drug molecules through the systemic route. Moreover, the abundant blood circulation in the fundus accelerates drug metabolism. To uphold the required drug concentration, patients must undergo frequent chemotherapy sessions.
UNASSIGNED: To address these challenges above, we need to develop a secure and effective drug delivery system (FA-PEG-PDA-DOX) for the fundus.
UNASSIGNED: We offered superior therapeutic efficacy with minimal or no side effects and successfully established orthotopic mouse models. We evaluated cellular uptake performance and targeting efficiency of FA-PEG-PDA-DOX nanosystem and assessed its synergistic antitumor effects in vitro and vivo. Biodistribution assessments were performed to determine the retention time and targeting efficiency of the NPs in vivo. Additionally, safety assessments were conducted.
UNASSIGNED: Cell endocytosis rates of the FA-PEG-PDA-DOX+Laser group became 5.23 times that of the DOX group and 2.28 times that of FA-PEG-PDA-DOX group without irradiation. The fluorescence signal of FA-PEG-PDA-DOX persisted for more than 120 hours at the tumor site. The number of tumor cells (17.2%) in the proliferative cycle decreased by 61.6% in the photothermal-chemotherapy group, in contrast to that of the saline control group (78.8%). FA-PEG-PDA-DOX nanoparticles(NPs) exhibited favorable biosafety and high biocompatibility.
UNASSIGNED: The dual functional targeted nanosystem, with the effects of DOX and mild-temperature elevation by irradiation, resulted in precise chemo/photothermal therapy in nude mice model.