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Zhou Z.,University of California at Santa Barbara | Zhou Z.,CAS Tianjin Institute of Biomedical Engineering | Anselmo A.C.,University of California at Santa Barbara | Mitragotri S.,University of California at Santa Barbara
Advanced Materials | Year: 2013

Nanorods provide distinct advantages over their spherical counterparts for targeted drug delivery. Here, a novel method is described for the synthesis of biocompatible protein nanorods from spherical polystyrene templates using the layer-by-layer (LBL) technique. These nanorods can be used as a vehicle for the delivery of therapeutic agents to diseased sites. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ma Y.,Tsinghua University | Huang L.,Tsinghua University | Song C.,CAS Tianjin Institute of Biomedical Engineering | Zeng X.,Nankai University | And 2 more authors.
Polymer | Year: 2010

Cervical cancer remains a critical problem that is second only to breast cancer affecting women worldwide. The objective of this study was to develop formulation of docetaxel-loaded biodegradable poly(e{open}-caprolactone-co-lactide)-d-α-tocopheryl polyethylene glycol 1000 succinate (PCL-PLA-TPGS) nanoparticles for cervical cancer chemotherapy. A novel random copolymer, PCL-PLA-TPGS, was synthesized from e{open}-caprolactone, lactide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization. The obtained polymers were characterized by 1H NMR, FTIR, GPC and TGA. The docetaxel-loaded PCL-PLA-TPGS nanoparticles were prepared by a modified solvent extraction/evaporation technique and characterized in terms of size and size distribution, morphology, surface charge and physical state of encapsulated docetaxel. Cellular uptake and in vitro cytotoxicity of nanoparticle formulations were done in comparison with commercial formulation Taxotere® to investigate the efficacy of PCL-PLA-TPGS nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated with CLSM, demonstrating the coumarin 6-loaded PCL-PLA-TPGS nanoparticles could be internalized by Hela cells. In vitro cancer cell viability experiment showed that judged by IC50, the PCL-PLA-TPGS nanoparticle formulation was found to be more effective in cell number reduction than the Taxotere® after 48 h (p < 0.05), 72 h (p < 0.05) treatment. In conclusion, the PCL-PLA-TPGS copolymer could be acted as a novel and promising biologically active polymeric matrix material for nanoparticle formulation in cervical cancer treatment. © 2010 Elsevier Ltd.

Gao J.,Nankai University | Zheng W.,Nankai University | Zhang J.,Nankai University | Guan D.,Nankai University | And 4 more authors.
Chemical Communications | Year: 2013

A β-galactosidase-responsive molecular hydrogelator of a nitric oxide (NO) donor can release NO in a controllable manner to improve wound healing. © 2013 The Royal Society of Chemistry.

Li C.,CAS Tianjin Institute of Biomedical Engineering | Kong D.,CAS Tianjin Institute of Biomedical Engineering
Pharmacology and Therapeutics | Year: 2014

Epidemiological studies have identified positive associations between diabetes, obesity and cancer. Insulin, metformin and thiazolidinediones (TDZs) are among the major diabetes therapies that improve glycaemic control by acting via molecular targets including the insulin receptor and insulin-like growth factor pathways, adenosine monophosphate-activated kinase and peroxisome proliferator-activated receptor γ. It is well-established that clinical application of insulin and TDZs is associated with weight gain, but the potential of these therapies to promote tumourigenesis is less well-studied. In addition, although anti-tumour properties of metformin have been proposed, recently published data do not support a protective effect of metformin against cancer in diabetic patients. Given that diabetes and cancer each account for 8% and 13% of global deaths and there is a substantial financial burden incurred by both disorders, developing diabetes therapies that are safe, efficacious and cost-effective has never been more desirable. This timely review examines recent progress in delineating the molecular mechanisms responsible for the anti-diabetic actions of insulin, metformin and TZDs and considers evidence implicating these therapies in cell transformation and tumourigenesis. In addition, since the endocannabinoid signalling system (ECS) is now considered a therapeutic target and biomarker candidate for hyperglycaemia, obesity and cell growth, a brief section covering recent scientific advances regarding the ECS, particularly its functions in regulating glucose metabolism and cell survival, is also included in this review. © 2014 Elsevier Inc.

Wang W.,CAS Tianjin Institute of Biomedical Engineering | Li C.,CAS Tianjin Institute of Biomedical Engineering | Zhang J.,CAS Tianjin Institute of Biomedical Engineering | Dong A.,Tianjin University | Kong D.,CAS Tianjin Institute of Biomedical Engineering
Journal of Materials Chemistry B | Year: 2014

The therapeutic efficacy of gemcitabine is severely compromised by its rapid plasma degradation and low tumor-targeting efficiency. Furthermore, the hydrophilic properties of gemcitabine also make efficient encapsulation and in vivo release of the compound difficult in a nanoscale drug delivery system. Herein, gemcitabine-poly(methyl methacrylate) (Gem-PMMA) conjugated amphiphiles were prepared from a gemcitabine-bearing trithiocarbonate initiator via reversible addition-fragmentation chain transfer (RAFT) polymerization. The prodrug conjugate with a high drug payload can self-assemble in water into nanoparticles with an average diameter of 130 nm. In addition, gemcitabine molecules within the Gem-PMMA nanoparticles mainly exist in an amorphous state, implicating better gemcitabine release. Indeed, the releasing kinetics of gemcitabine was pH-dependent and a controlled release of gemcitabine from the nanoparticles was observed with 71.6% of cumulative drug release in 72 h in the presence of protease cathepsin B. The cytotoxicity of the gemcitabine prodrug nanoparticles was evident as demonstrated by an in vitro viability assay using human pulmonary carcinoma, A549, and breast cancer cells, MCF-7. In vivo assessment of the gemcitabine-loaded nanoparticles using BALB/c nude mice with A549 cell derived xenograft tumors indicated that these intravenously administered nanoparticles efficiently inhibit tumor growth as well as alleviate the drug-associated side effects at a dose of 26 mg kg-1. In summary a prodrug nanoparticle, Gem-PMMA, with excellent delivery efficiency and tumor growth inhibition efficacy, was designed and produced. Our results demonstrated the potential of the gemcitabine prodrug nanoparticles as a promising therapeutic formulation for chemotherapy. © 2014 The Royal Society of Chemistry.

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