Lin Min, Liu Xiumei, Li Jing, Zou Hong, Wang Jie, Yan Zi, Liu Ying, Lyu Yaqi, Feng Nianping
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Department of Ophthalmology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Theranostics. 2025 Mar 10;15(9):3995-4015. doi: 10.7150/thno.108471. eCollection 2025.
Retinoblastoma is one of the most aggressive paediatric cancers originating from retina and finally invades vitreous humour or other tissues if treated improperly. Current interventions often fail due to the complexities of tumour progression and drug resistance driven by frequent intravitreal injection and epithelial-mesenchymal transition (EMT). Consequently, there is an unmet need for more effective, less invasive treatments. A near-infrared (NIR)-responsive liposome/hydrogel platform that incorporates quercetin (QUE) and doxorubicin (DOX) co-loaded liposomes (QD Lipo), and indocyanine green (ICG) in a low-gelling temperature agarose hydrogel (LAgel) was developed to improve efficacy through localized, on-demand delivery of chemo-photothermal therapy directly at the site of tumour. The initial phase of the study examined the injectability, reversibility and stability of QD Lipo/ICG/LAgel under NIR using -SEM technique and rheological measurement. Following this, photothermal conversion capability and controlled release of QD Lipo, alongside the mobility and penetration of QD Lipo was investigated using infrared thermal imaging, nanoparticle tracking analysis and fluorescence microscope. Moreover, retinoblastoma orthotopic model was established to corroborate the anti-tumour effectiveness . Flow cytometry, H&E, immunohistochemical staining, animal imaging and western blotting were performed to identify the underling mechanism of QD Lipo/ICG/LAgel to improve the treatment. The thermosensitivity and photothermal conversion capabilities of QD Lipo/ICG/LAgel enable precise, on-demand drug delivery in vitreous, significantly reducing the need for frequent intravitreal injections. and evaluation demonstrated that with facilitation of QUE, our platform effectively targets the rapid tumour progression and overcome therapeutic resistance of mild photothermal therapy (PTT), by modulating EMT process and inhibiting heat shock protein (HSP) level. This innovative approach not only mitigates the current challenges of repeated invasive medication, but also sets new strategies for treating complex ocular diseases.
视网膜母细胞瘤是起源于视网膜的侵袭性最强的儿科癌症之一，如果治疗不当，最终会侵犯玻璃体或其他组织。由于频繁玻璃体内注射和上皮-间质转化（EMT）导致肿瘤进展和耐药性的复杂性，目前的干预措施往往失败。因此，迫切需要更有效、侵入性更小的治疗方法。开发了一种近红外（NIR）响应脂质体/水凝胶平台，该平台将槲皮素（QUE）和阿霉素（DOX）共载脂质体（QD脂质体）以及吲哚菁绿（ICG）整合到低凝胶温度琼脂糖水凝胶（LAgel）中，通过在肿瘤部位直接进行局部按需化疗光热疗法来提高疗效。该研究的初始阶段使用扫描电子显微镜（SEM）技术和流变学测量方法，检测了QD脂质体/ICG/LAgel在近红外光下的可注射性、可逆性和稳定性。在此之后，使用红外热成像、纳米颗粒跟踪分析和荧光显微镜研究了QD脂质体的光热转换能力和控释性能，以及QD脂质体的流动性和穿透性。此外，还建立了视网膜母细胞瘤原位模型以证实其抗肿瘤效果。通过流式细胞术、苏木精-伊红染色（H&E）、免疫组织化学染色、动物成像和蛋白质免疫印迹法来确定QD脂质体/ICG/LAgel改善治疗效果的潜在机制。QD脂质体/ICG/LAgel的热敏感性和光热转换能力能够在玻璃体内实现精确的按需药物递送，显著减少了频繁玻璃体内注射的需求。评估表明，在QUE的促进作用下，我们的平台通过调节EMT过程和抑制热休克蛋白（HSP）水平，有效地靶向快速肿瘤进展并克服了温和光热疗法（PTT）的治疗抗性。这种创新方法不仅缓解了当前重复侵入性用药的挑战，还为治疗复杂眼部疾病制定了新策略。
