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Near-Infrared Laser-Driven in Situ Self-Assembly as a General Strategy for Deep Tumor Therapy
Nano Letters ( IF 10.8 ) Pub Date : 2018-09-25 00:00:00 , DOI: 10.1021/acs.nanolett.8b03174
Fu-Hua Liu 1 , Yong Cong 1 , Guo-Bin Qi 1 , Lei Ji 1 , Zeng-Ying Qiao 1 , Hao Wang 1
Affiliation  

Nanotherapeutics have encountered some bottleneck problems in cancer therapy, such as poor penetration and inefficient accumulation in tumor site. We herein developed a novel strategy for deep tissue penetration in molecular level and near-infrared (NIR) laser guided in situ self-assembly to solve these challenges. For the proof-of-concept study, we synthesized the polymer–peptide conjugates (PPCs) composed of (i) poly(β-thioester) as thermoresponsive backbone, (ii) functional peptides (cytotoxic peptide and cell-penetrating peptide), and (iii) the NIR molecule with photothermal property. The PPCs in the molecular level with small size (<10 nm) can penetrate deeply into the interior of the tumor at body temperature. Under the irradiation of NIR laser, the temperature rise induced by photothermal molecules led to the intratumoral self-assembly of thermoresponsive PPCs. The resultant spherical nanoparticles can accumulate in tumor and enter cells effectively, inducing cell apoptosis by destroying mitochondria membrane. Through the site-specific size control, a variety of merits of PPCs are realized including deep tumor penetration, enhanced accumulation, and cellular internalization in vivo. Taking advantage of the NIR guided in situ assembly strategy, numerous polymeric or nanoscaled therapeutics with high anticancer activity can be exploited.

中文翻译:

近红外激光驱动原位自组装作为深部肿瘤治疗的一般策略

纳米疗法在癌症治疗中遇到了一些瓶颈问题,例如渗透力差和在肿瘤部位的积聚效率低下。我们在这里为分子水平的深层组织穿透和近红外(NIR)激光引导的原位自组装开发了一种新颖的策略,以解决这些挑战。对于概念验证研究,我们合成了聚合物-肽结合物(PPC),该结合物由(i)聚(β-硫酯)作为热响应性骨架,(ii)功能性肽(细胞毒性肽和可穿透细胞的肽)和(iii)具有光热性质的NIR分子。在体温下,分子水平较小(<10 nm)的PPC可以深入渗透到肿瘤内部。在近红外激光的照射下 光热分子引起的温度升高导致热响应性PPC在肿瘤内自组装。所得球形纳米颗粒可在肿瘤中积累并有效进入细胞,通过破坏线粒体膜诱导细胞凋亡。通过特定位置的大小控制,实现了PPC的多种优点,包括深层肿瘤渗透,增强的积累和体内细胞内在化。利用NIR指导的原位组装策略,可以开发出许多具有高抗癌活性的聚合物或纳米级治疗剂。实现了PPC的多种优点,包括深层肿瘤渗透,增强的积累和体内细胞内在化。利用NIR指导的原位组装策略,可以开发出许多具有高抗癌活性的聚合物或纳米级治疗剂。实现了PPC的多种优点,包括深层肿瘤渗透,增强的积累和体内细胞内在化。利用NIR指导的原位组装策略,可以开发出许多具有高抗癌活性的聚合物或纳米级治疗剂。
更新日期:2018-09-25
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