Department of Urology, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210009, China.
School of Pharmacy, Nantong University, Nantong, 226001, China.
J Nanobiotechnology. 2020 Sep 4;18(1):124. doi: 10.1186/s12951-020-00686-3.
Chemotherapy is a standard cancer treatment which uses anti-cancer drugs to destroy or slow the growth of cancer cells. However, chemotherapy has limited therapeutic effects in bladder cancer. One of the reasons of this resistance to chemotherapy is that higher levels of glutathione in invasive bladder cancer cells. We have fabricated nanoparticles that respond to high concentrations of glutathione and near-infrared laser irradiation in order to increase the drug accumulation at the tumor sites and combine chemotherapy with photothermal therapy to overcome the challenges of bladder cancer treatment.
The DOX&IR780@PEG-PCL-SS NPs were prepared by co-precipitation method. We investigated the tumor targeting capability of NPs in vitro and in vivo. The orthotopic bladder cancer model in C57BL/6 mice was established for in vivo study and the photothermal effects and therapeutic efficacy of NPs were evaluated.
The DOX&IR780@PEG-PCL-SS NPs were synthesized using internal cross-linking strategy to increase the stability of nanoparticles. Nanoparticles can be ingested by tumor cells in a short time. The DOX&IR780@PEG-PCL-SS NPs have dual sensitivity to high levels of glutathione in bladder cancer cells and near-infrared laser irradiation. Glutathione triggers chemical structural changes of nanoparticles and preliminarily releases drugs, Near-infrared laser irradiation can promote the complete release of the drugs from the nanoparticles and induce a photothermal effect, leading to destroying the tumor cells. Given the excellent tumor-targeting ability and negligible toxicity to normal tissue, DOX&IR780@PEG-PCL-SS NPs can greatly increase the concentration of the anti-cancer drugs in tumor cells. The mice treated with DOX&IR780@PEG-PCL-SS NPs have a significant reduction in tumor volume. The DOX&IR780@PEG-PCL-SS NPs can be tracked by in vivo imaging system and have good tumor targeting ability, to facilitate our assessment during the experiment.
A nanoparticle delivery system with dual sensitivity to glutathione and near-infrared laser irradiation was developed for delivering IR780 and DOX. Chemo-photothermal synergistic therapy of both primary bladder cancer and their metastases was achieved using this advanced delivery system.
化疗是一种标准的癌症治疗方法，它使用抗癌药物来破坏或减缓癌细胞的生长。然而，化疗对膀胱癌的治疗效果有限。膀胱癌对化疗产生耐药性的原因之一是侵袭性膀胱癌细胞中谷胱甘肽水平较高。我们已经制备了纳米粒子，这些纳米粒子可以响应高浓度的谷胱甘肽和近红外激光辐射，以便增加药物在肿瘤部位的积累，并将化疗与光热疗法相结合，克服膀胱癌治疗的挑战。
采用共沉淀法制备 DOX&IR780@PEG-PCL-SS NPs。我们研究了 NPs 在体外和体内的肿瘤靶向能力。在 C57BL/6 小鼠中建立了原位膀胱癌模型，用于体内研究，并评价了 NPs 的光热效应和治疗效果。
采用内部交联策略合成了 DOX&IR780@PEG-PCL-SS NPs，以增加纳米粒子的稳定性。纳米粒子可以在短时间内被肿瘤细胞摄取。DOX&IR780@PEG-PCL-SS NPs 对膀胱癌细胞中高水平的谷胱甘肽和近红外激光辐射具有双重敏感性。谷胱甘肽触发纳米粒子的化学结构变化，并初步释放药物，近红外激光辐射可以促进药物从纳米粒子中完全释放，并诱导光热效应，导致肿瘤细胞破坏。由于具有优异的肿瘤靶向能力和对正常组织的低毒性，DOX&IR780@PEG-PCL-SS NPs 可以大大增加肿瘤细胞中抗癌药物的浓度。用 DOX&IR780@PEG-PCL-SS NPs 治疗的小鼠肿瘤体积显著减小。DOX&IR780@PEG-PCL-SS NPs 可以通过体内成像系统进行跟踪，具有良好的肿瘤靶向能力，便于我们在实验过程中进行评估。
开发了一种对谷胱甘肽和近红外激光辐射具有双重敏感性的纳米粒子递送系统，用于递送 IR780 和 DOX。使用这种先进的递送系统实现了原发性膀胱癌及其转移灶的化疗-光热协同治疗。
