Bhavsar Dhaval B, Patel Vijay, Sawant Krutika K
Pharmacy Department, G. H. Patel Pharmacy Building, The M. S. University of Baroda, Fatehgunj, Vadodara 390002, Gujarat, India.
Animal Disease Investigation Unit, Alembic Road, Opp. Model Farm, Vadodara, 390 003, Gujarat, India.
Eur J Pharm Sci. 2020 Sep 1;152:105428. doi: 10.1016/j.ejps.2020.105428. Epub 2020 Jun 15.
The main reason for limited efficacy of anticancer drug is the poor accretion of administered amount of drug within the tumor. Here, chitosan folate capped dual responsive mesoporous silica nanoparticles (MSNs) which can actively target cancer cells, and provide burst release of loaded anticancer drug within tumor cells and ultimately leading to improved therapeutic efficacy were synthesized. MSNs were synthesized using most economic silica source, sodium silicate. Doxorubicin (DOX) was loaded within the pores of MSNs and these drug loaded MSNs were first reacted with cystamine dihydrochloride followed by capping with chitosan-folate conjugate (CH-FA) to produce dual (redox and pH) responsive nanoparticles with the ability to actively target breast cancer cells. A triggered release of DOX from MSNs under acidic redox (pH 5.5, 10 mM GSH) environment was confirmed by in vitro release studies. The formulation exhibited 2.14 and 1.65 folds higher cytotoxicity than free drug against MCF-7 and MDA-MB-231 cells. DOX-MSN-SS-CH-FA showed superior tumor suppressing activity as compared to DOX-MSN or DOX alone in the treatment of Ehrlich Ascites Carcinoma (EAC) induced breast cancer with significantly reduced hematological and organ specific toxicities associated with DOX treatment.
抗癌药物疗效有限的主要原因是肿瘤内给药量的累积不佳。在此，合成了壳聚糖叶酸包覆的双响应介孔二氧化硅纳米颗粒（MSNs），其可主动靶向癌细胞，并在肿瘤细胞内实现负载抗癌药物的突发释放，最终提高治疗效果。MSNs使用最经济的硅源硅酸钠合成。阿霉素（DOX）负载于MSNs的孔内，这些载药MSNs首先与二盐酸半胱胺反应，然后用壳聚糖 - 叶酸共轭物（CH - FA）包覆，以制备具有主动靶向乳腺癌细胞能力的双（氧化还原和pH）响应纳米颗粒。体外释放研究证实了在酸性氧化还原（pH 5.5，10 mM GSH）环境下DOX从MSNs的触发释放。该制剂对MCF - 7和MDA - MB - 231细胞的细胞毒性比游离药物分别高2.14倍和1.65倍。在治疗艾氏腹水癌（EAC）诱导的乳腺癌中，DOX - MSN - SS - CH - FA与DOX - MSN或单独的DOX相比显示出优异的肿瘤抑制活性，且与DOX治疗相关的血液学和器官特异性毒性显著降低。
