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Stem Cell-Based Delivery of Gold/Chlorin e6 Nanocomplexes for Combined Photothermal and Photodynamic Therapy.
ACS Applied Materials & Interfaces ( IF 9.5 ) Pub Date : 2020-06-29 , DOI: 10.1021/acsami.0c03446
Chun-Chiao Chuang,Yi-Ning Chen,Yi-Ya Wang,Yu-Chen Huang,Ssu-Yu Lin,Rih-Yang Huang,Yu-Yun Jang,Chun-Chi Yang,Yu-Fen Huang,Chien-Wen Chang

Combining photothermal and photodynamic modalities has shown encouraging therapeutic efficacy against various malignant cancers. Developing a delivery method for targeting and penetrating tumors is still a major focus for advancing this therapeutic approach. Herein, we report a novel strategy involving the utilization of stem cells as a live carrier to codeliver photothermal and photodynamic agents for cancer therapy. To this end, a novel gold nanorod (AuNR)-PEG-PEI (APP)/chlorin e6 (Ce6)-loaded adipose-derived stem cell (ADSC) system is proposed in which AuNRs and Ce6 act as the photothermal and photodynamic agents, respectively. To integrate with stem cells, the APP/Ce6 nanocomplexes exhibit advantages of low drug leakage, low cytotoxicity, efficient cellular uptake, and redox-responsive release. After loading of APP/Ce6 nanocomplexes, the ADSCs still maintained good tumor tropism and were capable of penetrating into the tumor spheroids. The photothermal effect induced by exposure to near-infrared light irradiation at 808 nm promoted the release of Ce6 from the stem cells into the surroundings and hence increased its availability to treat cancer cells. APP/Ce6-loaded ADSCs exerted effective dose-dependent in vitro anticancer activities via anticipated photothermal and photodynamic effects. In a murine CT26 colon cancer model, APP/Ce6 delivered by ADSCs resulted in superior tumor suppression compared to other delivery strategies. It was also noted that in vivo applications of APP/Ce6-loaded ADSCs did not induce noticeable detrimental effects on normal tissues/organs.

中文翻译:

基于干细胞的Gold / Chlorin e6纳米复合物的递送,用于光热和光动力疗法的联合治疗。

结合光热和光动力方式已显示出令人鼓舞的针对各种恶性癌症的治疗功效。开发靶向和穿透肿瘤的递送方法仍然是推进这种治疗方法的主要重点。在这里,我们报告了一种新颖的策略,其中涉及利用干细胞作为活载体来编码用于癌症治疗的光热和光动力剂。为此,提出了一种新型的金纳米棒(AuNR)-PEG-PEI(APP)/二氢卟酚e6(Ce6)负载的脂肪干细胞(ADSC)系统,其中AuNRs和Ce6充当光热和光动力剂,分别。为了与干细胞整合,APP / Ce6纳米复合物展现出低药物泄漏,低细胞毒性,有效的细胞摄取和氧化还原反应性释放的优势。加载APP / Ce6纳米复合物后,ADSC仍然保持良好的肿瘤向性,并且能够渗透到肿瘤球体中。通过暴露于808 nm的近红外光辐射诱导的光热效应促进了Ce6从干细胞向周围环境的释放,因此增加了其治疗癌细胞的可用性。装载APP / Ce6的ADSC发挥有效的剂量依赖性通过预期的光热和光动力效应进行体外抗癌活性。在鼠类CT26结肠癌模型中,与其他递送策略相比,由ADSC递送的APP / Ce6可以抑制肿瘤。还应指出,在体内应用APP / Ce6的ADSC不会对正常组织/器官产生明显的有害作用。
更新日期:2020-07-08
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