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Hyaluronic acid wreathed, trio-stimuli receptive and on-demand triggerable nanoconstruct for anchored combinatorial cancer therapy.
Carbohydrate Polymers ( IF 11.2 ) Pub Date : 2020-08-01 , DOI: 10.1016/j.carbpol.2020.116815
Kishwor Poudel 1 , Asmita Banstola 2 , Tuan Hiep Tran 3 , Raj Kumar Thapa 1 , Milan Gautam 1 , Wenquan Ou 1 , Le Minh Pham 1 , Srijan Maharjan 1 , Jee-Heon Jeong 1 , Sae Kwang Ku 4 , Han-Gon Choi 5 , Chul Soon Yong 1 , Jong Oh Kim 1
Affiliation  

Hyaluronic acid (HA) assisted effective internalization into CD44 receptor-overexpressing cancer cells, which could offer an excellent cytotoxic profile and tumor alterations. In this study, duo-photothermal agents (copper sulfide (CuS) and graphene oxide (GO)), chemotherapeutic drug (doxorubicin (DOX)), and targeting moiety (HA) were incorporated into a complexed nanoconstruct for trio-responsive chemo-phototherapy. The nanosystem (CuS(DOX)-GO-HA) was demonstrating its responsive drug release and escalated photothermal behavior. The hyperthermia and photodynamic effect were observed along with efficient ROS generation in the presence of dual photosensitizers. The in vivo biodistribution and photothermal profile reflected a high accumulation and retention of the nanoconstruct in the tumor. Importantly, nanoconstructs effectively inhibit tumor growth based on tumor volume analysis and the altered expression of apoptosis, cell proliferation, and angiogenesis markers. Collectively, these findings suggest that this nanoconstruct has excellent antitumor effects in CD44 overexpressed cells showing the potential for clinical translation in the future.



中文翻译:

透明质酸花圈,三刺激接受和按需触发的纳米结构锚定组合癌症治疗。

透明质酸(HA)有助于有效内化到CD44受体过表达的癌细胞中,这可能会提供出色的细胞毒性特征和肿瘤改变。在这项研究中,将二重光热剂(硫化铜(CuS)和氧化石墨烯(GO)),化学治疗药物(阿霉素(DOX))和靶向部分(HA)掺入了复合纳米结构中,用于三重响应化学光疗。 。纳米系统(CuS(DOX)-GO-HA)展示了其响应性药物释放和逐步升级的光热行为。在双重光敏剂存在下,观察到热疗和光动力效应以及有效的ROS生成。在体内生物分布和光热分布反映了纳米结构在肿瘤中的高积累和保留。重要的是,基于肿瘤体积分析以及凋亡,细胞增殖和血管生成标记物表达的改变,纳米结构可有效抑制肿瘤的生长。总而言之,这些发现表明,这种纳米结构在CD44过表达的细胞中具有出色的抗肿瘤作用,显示出将来进行临床翻译的潜力。

更新日期:2020-08-11
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