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巯基化羧甲基葡聚糖作为hSET1反义寡核苷酸结肠递送的纳米载体:体外稳定性和效率研究

Thiolated carboxymethyl dextran as a nanocarrier for colon delivery of hSET1 antisense: In vitro stability and efficiency study.

作者信息

Kiani Melika, Mirzazadeh Tekie Farnaz Sadat, Dinarvand Meshkat, Soleimani Masoud, Dinarvand Rassoul, Atyabi Fatemeh

机构信息

Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran.

Stem Cell Technology Research Centre, P.O. Box 14155-3174, Tehran, Iran; Department of Hematology, School of Medical Sciences, Tarbiat Modares University, P.O. Box: 14115-111, Tehran, Iran.

出版信息

Mater Sci Eng C Mater Biol Appl. 2016 May;62:771-8. doi: 10.1016/j.msec.2016.02.009. Epub 2016 Feb 5.

Abstract

Gene therapy is an optimistic approach in cancer treatment. However, for efficient delivery of gene materials, designing an appropriate vector is necessary. Polyelectrolyte complexes (PECs) of chitosan and dextran could be considered a proper nanoparticulate carrier for sensitive biomaterials. In this study, PECs of chitosan and thiolated dextran were used as either an injectable or oral gene delivery system. hSET1 antisense was loaded into the PECs to suppress proliferation of colon cancer cell line. The prepared nanoparticles have ~115nm diameter size and positive zeta potential with high mucoadhesion properties. They are able to protect antisense from degradation in serum and biorelevant fluids (FaSSIF and FaSSGF). Furthermore, prepared nanoparticles demonstrated superior cellular penetration and inhibitory effect on SW480 colon cancer cell proliferation. All nanoparticles significantly down regulated hSET1 in comparison with naked antisense. It can be concluded that thiolated PECs have potential use for injectable or oral delivery of nucleic acids such as antisense.

摘要

基因治疗是癌症治疗中一种乐观的方法。然而,为了有效地递送基因材料,设计合适的载体是必要的。壳聚糖和葡聚糖的聚电解质复合物(PEC)可被认为是用于敏感生物材料的合适纳米颗粒载体。在本研究中,壳聚糖和硫醇化葡聚糖的PEC被用作注射或口服基因递送系统。将hSET1反义核酸负载到PEC中以抑制结肠癌细胞系的增殖。制备的纳米颗粒直径约为115nm,具有正的zeta电位和高粘膜粘附特性。它们能够保护反义核酸在血清和生物相关流体(FaSSIF和FaSSGF)中不被降解。此外,制备的纳米颗粒表现出优异的细胞穿透能力和对SW480结肠癌细胞增殖的抑制作用。与裸反义核酸相比,所有纳米颗粒均显著下调hSET1。可以得出结论,硫醇化PEC在注射或口服递送核酸如反义核酸方面具有潜在用途。

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