Department of Radiology First Hospital of China Medical University, No. 155 Nanjing North Road, Shenyang, 110001, P. R. China.
Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
Nanoscale. 2017 Mar 9;9(10):3429-3439. doi: 10.1039/c6nr09862b.
The use of nanomaterials as drug delivery systems shows good effects in treating tumors. However, the effective dose of drugs targeted to tumor tissues is very low because of the effect of the reticuloendothelial system (RES) in removing such foreign substances. In order to eliminate the RES effect, we developed mPEG-PLGA@ZrO@(DOX + ILS) (mPEG-PLGA@ZrO@[DOX + ILS]) drug-loaded microspheres. These microwave (MW)-sensitized microspheres directly embolized the blood-supply vessels of tumors to induce tumor ischemia and hypoxia, as well as to aggregate drugs within tumor tissues in a long-lasting manner. Additionally, combination with MW ablation can triple the effects for the inhibition of tumor growth. The MW sensitive ionic liquid (ILS) in microspheres can rapidly produce a high temperature in a MW field on the basis of MW sensitization, thus accelerating the degradation of microspheres to release DOX-loaded ZrO into the lesions to kill tumors. Microspheres can also prolong the pharmacological time and effect of drugs through the enhanced permeability and retention (EPR) effect of nanocarriers, as well as the sustained release of nanomaterials. Studies performed in vivo revealed that mPEG-PLGA@ZrO@(DOX + ILS) showed good biosafety. We undertook sensitized microsphere embolism therapy using novel mPEG-PLGA@ZrO@(DOX + ILS) microspheres in a rabbit VX liver tumor model. Three, 6 and 9 d after treatment, computed tomography indicated no significant change in tumor size, and diffusion weighted imaging showed a marked decrease of residual tumor tissues. With the multiple functions of inducing embolisms, sensitization, and the sustained release of chemotherapeutics, novel mPEG-PLGA@ZrO@(DOX + ILS) microspheres can achieve good therapeutic efficacy, in combination with MW ablation and chemotherapy, while embolizing the blood vessels of arterial tumors.
纳米材料作为药物传递系统在治疗肿瘤方面显示出良好的效果。然而，由于网状内皮系统（RES）对这些异物的清除作用，靶向肿瘤组织的药物的有效剂量非常低。为了消除 RES 效应，我们开发了 mPEG-PLGA@ZrO@（DOX+ILS）（mPEG-PLGA@ZrO@[DOX+ILS]）载药微球。这些微波（MW）敏化微球直接栓塞肿瘤的供血血管，诱导肿瘤缺血缺氧，并将药物在肿瘤组织中长时间聚集。此外，与 MW 消融相结合，可以使肿瘤生长抑制效果提高三倍。微球中的 MW 敏感离子液体（ILS）可以在 MW 敏化的基础上，在 MW 场中迅速产生高温，从而加速微球的降解，将负载 DOX 的 ZrO 释放到病变部位杀死肿瘤。微球还可以通过纳米载体的增强渗透和保留（EPR）效应以及纳米材料的持续释放来延长药物的药代动力学时间和效果。体内研究表明，mPEG-PLGA@ZrO@（DOX+ILS）表现出良好的生物安全性。我们在兔 VX 肝癌模型中进行了新型 mPEG-PLGA@ZrO@（DOX+ILS）微球的敏化微球栓塞治疗。治疗后 3、6 和 9d，CT 提示肿瘤大小无明显变化，弥散加权成像显示残余肿瘤组织明显减少。新型 mPEG-PLGA@ZrO@（DOX+ILS）微球具有诱导栓塞、敏化和持续释放化疗药物的多种功能，与 MW 消融和化疗相结合，可栓塞动脉肿瘤的血管，达到良好的治疗效果。
