International Journal of Nanomedicine (Apr 2017)
Magnetic and pH dual-responsive mesoporous silica nanocomposites for effective and low-toxic photodynamic therapy
Abstract
Jieqiong Zhan,1,2,* Zhiqiang Ma,2,* Dan Wang,3 Xinfang Li,2 Xiangui Li,2 Lijing Le,2 Anfeng Kang,2 Pengwei Hu,1 Lan She,2 Feng Yang1,2 1Department of Pharmacy, Hebei North University, Zhangjiakou, Hebei, 2Department of Inorganic Chemistry, School of Pharmacy, 3Department of Obstetrics and Gynecology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Nonspecific targeting, large doses and phototoxicity severely hamper the clinical effect of photodynamic therapy (PDT). In this work, superparamagnetic Fe3O4 mesoporous silica nanoparticles grafted by pH-responsive block polymer polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) were fabricated to load the model photosensitizer rose bengal (RB) in the aim of enhancing the efficiency of PDT. Compared to free RB, the nanocomposites (polyethylene glycol-b-polyaspartate-modified rose bengal-loaded magnetic mesoporous silica [RB–MMSNs]) could greatly enhance the cellular uptake due to their effective endocytosis by mouse melanoma B16 cell and exhibited higher induced apoptosis although with little dark toxicity. RB–MMSNs had little dark toxicity and even much could be facilitated by magnetic field in vitro. RB–MMSNs demonstrated 10 times induced apoptosis efficiency than that of free RB at the same RB concentration, both by cell counting kit-8 (CCK-8) result and apoptosis detection. Furthermore, RB–MMSNs-mediated PDT in vivo on tumor-bearing mice showed steady physical targeting of RB–MMSNs to the tumor site; tumor volumes were significantly reduced in the magnetic field with green light irradiation. More importantly, the survival time of tumor-bearing mice treated with RB–MMSNs was much prolonged. Henceforth, polyethylene glycol-b-polyaspartate-modified magnetic mesoporous silica (MMSNs) probably have great potential in clinical cancer photodynamic treatment because of their effective and low-toxic performance as photosensitizers’ vesicles. Keywords: magnetic mesoporous silica, rose bengal, polymer polyethylene glycol-b-poly(aspartic acid), magnetic targeting, pH responsive, photodynamic therapy