Search

Mei-Qi Xu,1,2 Yan-Li Hao,1,2 Jing-Ru Wang,1,2 Zhuo-Yue Li,1,2 Hui Li,1 Zhen-Han Feng,1,2 Hui Wang,1,2 Jing-Wen Wang,1,2 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of ChinaCorrespondence: Xuan ZhangDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing, 100191, People’s Republic of ChinaTel +86-10-82805765Fax +86-10-8280576Email xuanzhang@bjmu.edu.cnPurpose: Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-paclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo.Methods: We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated.Results: The size of ALA-PTX NPs was approximately 110.7± 1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5– 2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vi

Zhuo-Yue Li,1,2 Yi-Fan Yin,1,2 Yang Guo,1,2 Hui Li,1,2 Mei-Qi Xu,1,2 Man Liu,1,2 Jing-Ru Wang,1,2 Zhen-Han Feng,1,2 Xiao-Chuan Duan,1,2 Shuang Zhang,1,2 Shuai-Qiang Zhang,1,2 Guang-Xue Wang,2 Ai Liao,2 Shu-Min Wang,3 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 3Department of Ultrasound, Peking University Third Hospital, Peking University, Beijing 100191, People’s Republic of ChinaCorrespondence: Xuan ZhangDepartment of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Beijing 100191, People’s Republic of ChinaTel/Fax +86-10-82805765Email xuanzhang@bjmu.edu.cnShu-Min WangDepartment of Ultrasound, Peking University Third Hospital, Peking University, Xueyuan Road 38, Beijing 100191, People’s Republic of ChinaEmail shuminwang2014@163.comIntroduction: Because tumor-associated inflammation is a hallmark of cancer treatment, in the present study, sorafenib mesoporous silica nanomatrix (MSNM@SFN) co-administrated with flufenamic acid (FFA, a non-steroidal anti–inflammatory drug (NSAID)) was investigated to enhance the anti-tumor activity of MSNM@SFN.Methods: Metastatic breast tumor 4T1/luc cells and hepatocellular carcinoma HepG2 cells were selected as cell models. The effects of FFA in vitro on cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in 4T1/luc and HepG2 cells were investigated. The in vivo anti-tumor activity of MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) was evaluated in a 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model, respectively.Results: The results indicated that FFA could markedly decrease cell migr

Xiao-Chuan Duan,1,2,* Xin Yao,1,2,* Shuang Zhang,1,2 Mei-Qi Xu,1,2 Yan-Li Hao,1,2 Zhan-Tao Li,1,2 Xiu-Chai Zheng,2 Man Liu,1,2 Zhuo-Yue Li,1,2 Hui Li,1 Jing-Ru Wang,1,2 Zhen-Han Feng,1 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, People’s Republic of China *These authors contributed equally to this work Background: 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA-PTX) is a paclitaxel (PTX) bioreductive prodrug synthesized by our lab. We hypothesize that NPPA-PTX can self-assemble to form nanoparticles (NPs). Materials and methods: In the present research, the theoretical partition coefficient (XlogP) and Hansen solubility parameters of NPPA-PTX were calculated. NPPA-PTX nanoparticles prepared by NPPA-PTX and DSPE-PEG (NPPA-PTX:DSPE-PEG =1:0.1, w/w) (NPPA-PTX@PEG NPs) were prepared and characterized. The cellular uptake, in vitro antitumor activity, in vivo targeting effect, tumor distribution, in vivo antitumor activity, and safety of NPPA-PTX@PEG NPs were investigated. Results: Our results indicate that NPPA-PTX can self-assemble to form NPPA-PTX@PEG NPs. Both the cellular uptake and safety of NPPA-PTX@PEG NPs were higher than those of Taxol. NPPA-PTX@PEG NPs could target tumor tissues by a passive targeting effect. In tumor tissues, NPPA-PTX@PEG NPs could completely transform into active PTX. The in vivo antitumor activity of NPPA-PTX@PEG NPs was confirmed in MDA-MB-231 tumor-bearing nude mice. Conclusion: The bioreductive prodrug NPPA-PTX could self-assemble to form NPs. The safety and antitumor activity of NPPA-PTX@PEG were confirmed in our in vitro and in vivo experiments. The NPPA-PTX@PEG NPs developed in this study could offer a new way of preparing bioreductive prodrug, self-assembled NPs suit

Xiu-Chai Zheng,1,2,* Wei Ren,1,2,* Shuang Zhang,1,2 Ting Zhong,1,2 Xiao-Chuan Duan,1,2 Yi-Fan Yin,1,2 Mei-Qi Xu,1,2 Yan-Li Hao,1,2 Zhan-Tao Li,1,2 Hui Li,1,2 Man Liu,1,2 Zhuo-Yue Li,1,2 Xuan Zhang1,2 1Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China; 2Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing, People’s Republic of China *These authors contributed equally to this work Background: In the present study, the tumor-specific, pH-responsive peptide H7K(R2)2 -modified, theranostic liposome-containing paclitaxel (PTX) and superparamagnetic iron oxide nanoparticles (SPIO NPs), PTX/SPIO-SSL-H7K(R2)2, was prepared by using H7K(R2)2 as the targeting ligand, SPIO NPs as the magnetic resonance imaging (MRI) agent, PTX as antitumor drug. Methods: The PTX/SPIO-SSL-H7K(R2)2 was prepared by a thin film hydration method. The characteristics of PTX/SPIO-SSL-H7K(R2)2 were evaluated. The targeting effect, MRI, and antitumor activity of PTX/SPIO-SSL-H7K(R2)2 were investigated detail in vitro and in vivo in human breast carcinoma MDA-MB-231 cell models. Results: Our results of in vitro flow cytometry, in vivo imaging, and in vivo MR imaging confirmed the pH-responsive characteristic of H7K(R2)2 in MDA-MB-231 cell line in vitro and in vivo. The results of in vivo MRI and in vivo antitumor activity confirmed the theranostic effect of PTX/SPIO-SSL-H7K(R2)2 in MDA-MB-231 tumor-bearing model. Conclusion: Considering all our in vitro and in vivo results, we conclude that we developed targeting modified theranostic liposome which could achieve both role of antitumor and MRI. Keywords: tumor-specific pH-responsive peptide, paclitaxel, superparamagnetic iron oxide nanoparticles, liposome, theranostic efficiency