Department of Hematology and Oncology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran; Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Medicine, Faculty of Medicine, Istanbul Aydin University, Istanbul, Turkey.
Carbohydr Polym. 2022 Jan 15;276:118747. doi: 10.1016/j.carbpol.2021.118747. Epub 2021 Oct 17.
Combination therapy through simultaneous delivery of anti-cancer drugs and genes with nano-assembled structure has been proved to be a simple and effective approach for treating breast cancer. In this study, redox-sensitive folate-appended-polyethylenimine-β-cyclodextrin (roFPC) host-guest supramolecular nanoparticles (HGSNPs) were developed as a targeted co-delivery system of doxorubicin (Dox) and Human telomerase reverse transcriptase-small interfering RNA) hTERT siRNA) for potential cancer therapy. The nanotherapeutic system was prepared by loading adamantane-conjugated doxorubicin (Ad-Dox) into roFPC through the supramolecular assembly, followed by electrostatically-driven self-assembly between hTERT siRNA and roFPC/Ad-Dox. The roFPC' host-guest structures allow pH-dependent intracellular drug release in a sustained manner, as well as simultaneous and effective gene transfection. This co-delivery vector displayed combined anti-tumor properties of the Dox-enhanced gene transfection, good water-solubility, and biocompatibility, possesses considerably enhanced hemocompatibility, and especially targets folate receptor-positive cells only at low N/P levels to prompt effective cell apoptosis for cancer treatment.
通过纳米组装结构同时递送抗癌药物和基因的联合治疗已被证明是治疗乳腺癌的一种简单有效的方法。在这项研究中，开发了具有氧化还原敏感性的叶酸修饰的聚乙烯亚胺-β-环糊精（roFPC）主体-客体超分子纳米颗粒（HGSNPs）作为阿霉素（Dox）和人端粒酶逆转录酶小干扰 RNA（hTERT siRNA）的靶向共递药系统，用于潜在的癌症治疗。纳米治疗系统通过超分子组装将金刚烷偶联的阿霉素（Ad-Dox）载入 roFPC 中制备得到，随后通过静电作用在 hTERT siRNA 和 roFPC/Ad-Dox 之间进行自组装。roFPC 的主体-客体结构允许以持续的方式进行 pH 依赖性的细胞内药物释放，以及同时有效的基因转染。这种共递药载体显示出 Dox 增强基因转染的联合抗肿瘤特性、良好的水溶性和生物相容性，具有相当增强的血液相容性，并且特别仅在低 N/P 水平下靶向叶酸受体阳性细胞以促使有效的细胞凋亡用于癌症治疗。
