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A Trojan horse biomimetic delivery strategy using mesenchymal stem cells for PDT/PTT therapy against lung melanoma metastasis.
Biomaterials Science ( IF 6.6 ) Pub Date : 2019-12-18 , DOI: 10.1039/c9bm01401b
Xumei Ouyang 1 , Xiaoling Wang 2 , Heinz-Bernhard Kraatz 3 , Soha Ahmadi 3 , Jianqing Gao 4 , Yuanyuan Lv 5 , Xiaoyi Sun 5 , Yongzhuo Huang 6
Affiliation  

Mesenchymal stem cell (MSC)-based biomimetic delivery has been actively explored for drug accumulation and penetration into tumors by taking advantage of the tumor-tropic and penetration properties of MSCs. In this work, we further demonstrated the feasibility of MSC-mediated nano drug delivery, which was characterized by the "Trojan horse"-like transport via an endocytosis-exocytosis-endocytosis process between MSCs and cancer cells. Chlorin e6 (Ce6)-conjugated polydopamine nanoparticles (PDA-Ce6) were developed and loaded into the MSCs. Phototherapeutic agents are safe to the MSCs, and their very low dark toxicity causes no impairment of the inherent properties of MSCs, including tumor-homing ability. The MSCs loaded with PDA-Ce6 (MSC-PDA-Ce6) were able to target and penetrate into tumors and exocytose 60% of the payloads in 72 h. The released PDA-Ce6 NPs could penetrate deep and be re-endocytosed by the cancer cells. MSC-PDA-Ce6 tended to accumulate in the lungs and delivered PDA-Ce6 into the tumors after intravenous injection in the mouse model with lung melanoma metastasis. Phototoxicity can be selectively triggered in the tumors by sequentially treating with near-infrared irradiation to induce photodynamic therapy (PDT) and photothermal therapy (PTT). The MSC-based biomimetic delivery of PDA-Ce6 nanoparticles is a potential method for dual phototherapy against lung melanoma metastasis.

中文翻译:

使用间充质干细胞对肺部黑色素瘤转移进行PDT / PTT治疗的特洛伊木马仿生传递策略。

通过利用间质干细胞(MSC)的向肿瘤性和渗透特性,已经积极探索了基于间充质干细胞(MSC)的仿生传递,以用于药物蓄积和渗透到肿瘤中。在这项工作中,我们进一步证明了MSC介导的纳米药物递送的可行性,其特点是通过MSC和癌细胞之间的内吞-胞吐-内吞过程进行“特洛伊木马”式转运。开发了结合了氯霉素e6(Ce6)的聚多巴胺纳米颗粒(PDA-Ce6),并将其加载到MSC中。光疗剂对MSC是安全的,并且其极低的暗毒性不会损害MSC的固有特性,包括肿瘤归巢能力。装有PDA-Ce6(MSC-PDA-Ce6)的MSC能够在72小时内靶向并渗透到肿瘤中,并吞噬60%的有效载荷。释放的PDA-Ce6 NPs可能穿透深层并被癌细胞重新内吞。在具有肺黑色素瘤转移的小鼠模型中静脉注射后,MSC-PDA-Ce6倾向于在肺中积累,并将PDA-Ce6递送到肿瘤中。通过依次用近红外辐射进行治疗以诱导光动力疗法(PDT)和光热疗法(PTT),可以在肿瘤中选择性触发光毒性。PDA-Ce6纳米粒子的基于MSC的仿生传递是针对肺部黑色素瘤转移的双重光疗的一种潜在方法。通过依次用近红外辐射进行治疗以诱导光动力疗法(PDT)和光热疗法(PTT),可以在肿瘤中选择性触发光毒性。PDA-Ce6纳米粒子的基于MSC的仿生传递是针对肺部黑色素瘤转移的双重光疗的一种潜在方法。通过依次用近红外辐射治疗以诱导光动力疗法(PDT)和光热疗法(PTT),可以在肿瘤中选择性触发光毒性。PDA-Ce6纳米粒子的基于MSC的仿生传递是针对肺部黑色素瘤转移的双重光疗的一种潜在方法。
更新日期:2020-02-19
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