Suchergebnisse

Huan Wang,1,2,* Xiangui Li,1,* Zhiqiang Ma,1 Dan Wang,3 Linzhao Wang,1,2 Jieqiong Zhan,1,4 Lan She,1 Feng Yang1 1Department of Inorganic Chemistry, School of Pharmacy, Second Military Medical University, Shanghai, 2Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, 3Department of Obstetrics and Gynecology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, 4Department of Pharmacy, Hebei North University, Zhangjiakou, Hebei, People's Republic of China *These authors contributed equally to this article Abstract: In this study, a highly effective transmembrane delivery vehicle based on PEGylated oxidized mesoporous carbon nanosphere (oMCN@PEG) was successfully fabricated in a facile strategy. oMCN@PEG exhibited a narrow size distribution of 90 nm, excellent hydrophilicity, good biocompatibility, and a very high loading efficiency for doxorubicin (DOX). The drug system (oMCN@DOX@PEG) exhibited excellent stability under neutral pH conditions, but with dramatic releases of DOX at reduced pH conditions. Pharmacokinetics study revealed that oMCN@DOX@PEG could prolong the circulation of DOX in the blood stream. The endocytosis, cytotoxicity, and anticancer effect in vitro and in vivo of the drug-loaded nanoparticles were also evaluated. Our results showed that the nanoparticles efficiently penetrated the membrane of tumor cells, subsequently released drugs, and efficiently inhibited the growth of cancer cells both in vitro and in vivo. Especially, oMCN@DOX@PEG also exhibited significant antimetastasis effect in advanced stage of malignant cancer, improving the survival time of tumor-bearing mice. The results suggested that oMCN@PEG might be a promising anticancer drug delivery vehicle for cancer therapy. Keywords: drug delivery, hydrophilic, mesoporous carbon nanoparticles, tumor metastasis

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

Zhiqiang Ma,*,1 Pengwei Hu,*,2 Changyong Guo,2 Dan Wang,3 Xingjie Zhang,1 Min Chen,1 Qirong Wang,1 Miao Sun,1 Peiyu Zeng,1 Fengkun Lu,1,2 Linhong Sun,1 Lan She,1 Hongtao Zhang,4 Jianzhong Yao,1 Feng Yang1,21School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China; 2Department of Pharmacy, Hebei North University, Zhangjiakou, People's Republic of China; 3Department of Obstetrics and Gynecology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China; 4Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, People's Republic China*These authors contributed equally to this workBackground: Nonspecific tumor targeting, potential relapse and metastasis of tumor after treatment are the main barriers in clinical photodynamic therapy (PDT) for cancer, hence, inhibiting relapse and metastasis of tumor is significant issues in clinic.Purpose: In this work, chidamide as a histone deacetylases inhibitor (HADCi) was bound onto a pH-responsive block polymer folate polyethylene glycol-b-poly(aspartic acid) (PEG-b-PAsp) grafted folate (FA-PEG-b-PAsp) to obtain the block polymer folate polyethylene glycol-b-poly(asparaginyl-chidamide) (FA-PEG-b-PAsp-chidamide, FPPC) as multimodal tumor-targeting drug-delivery carrier to inhibiting tumor cell proliferation and tumor metastasis in mice.Methods: Model photosensitizer pyropheophorbide-a (Pha) was encapsulated by FPPC in PBS to form the polymer micelles Pha@FPPC [folate polyethylene glycol-b-poly(asparaginyl-chidamide) micelles encapsulating Pha]. Pha@FPPC was characterized by transmission electron microscope and dynamic light scattering; also, antitumor activity in vivo and in vitro were investigated by determination of cellular ROS level, detection of cell apoptosis and cell cycle arrest, PDT antitumor activity in vivo and histological analysis.Results: With favorable and stable sphere morphology under transmission electron microscope (TEM) (∼93.0 nm), Pha@FPPC greatly enhanced the cellular uptake due to its folate-mediated effective endocytosis by mouse melanoma B16-F10 cells and the yield of ROS in tumor cells induced by PDT, and mainly caused necrocytosis and blocked cell growth cycle not only in G2 phase but also in G1/G0 phase after PDT. Pha@FPPC exhibited lower dark cytotoxicity in vitro and a better therapeutic index because of its higher dark cytotoxicity/photocytotoxicity ratio. Moreover, Pha@FPPC not only significantly inhibited the growth of implanted tumor and prolonged the survival time of melanoma-bearing mice due to both its folate-mediated tumor-targeting and selectively accumulation at tumor site by EPR (enhanced permeability and retention)effect as micelle nanoparticles but also remarkably prevented pulmonary metastasis of mice melanoma after PDT compared to free Pha, demonstrating its dual antitumor characteristics of PDT and HDACi.Conclusion: As a folate-mediated and acid-activated chidamide-grafted drug-delivery carrier, FPPC may have great potential to inhibit tumor metastasis in clinical photodynamic treatment for cancer because of its effective and multimodal tumor-targeting performance as photosensitizer vehicle.Keywords: photodynamic therapy, PDT, histone deacetylase inhibitor, HDACi, micelles, folate, pH-responsive, photosensitizer