CAS Tianjin Institute of Biomedical Engineering

Tianjin, China

CAS Tianjin Institute of Biomedical Engineering

Tianjin, China

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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.


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.


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.


Lv F.,CAS Tianjin Institute of Biomedical Engineering | He X.,CAS Tianjin Institute of Biomedical Engineering | Lu L.,CAS Tianjin Institute of Biomedical Engineering | Wu L.,CAS Tianjin Institute of Biomedical Engineering | Liu T.,CAS Tianjin Institute of Biomedical Engineering
Journal of Porphyrins and Phthalocyanines | Year: 2012

In order to develop a novel near infrared fluorescence agent, glucose conjugated zinc phthalocyanine, [2,9(10),16(17),23(24)-tetrakis((1-(β-D- glucopyranose-2-yl)-1H-1,2,3-triazol-4-yl)methoxyl)phthalocyaninato]zinc(II), was synthesized via Click reaction. Their chemical structures were characterized by mass spectrometry, nuclear magnetic resonance spectrum. Their light stability and fluorescence quantum yield were evaluated by UV-visible and fluorescent spectroscopic method. Optical imaging in vivo was performed with this saccharide conjugated phthalocyanine as probe on liver tumor-bearing nude mice. Near-infrared imaging effect, organ aggregation as well as distribution of probe in vivo were evaluated by in vivo fluorescence imaging technique. Results show that glucose conjugated zinc phthalocyanine has favorable water solubility, good optical stability and high emission ability in near infrared region. Imaging results demonstrate that saccharide conjugated phthalocyanine has possess obvious imaging effect in vivo, which implies its potential in cancer diagnosis as near infrared optical probe. © 2012 World Scientific Publishing Company.


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.


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.


Jiang L.,CAS Tianjin Institute of Biomedical Engineering | Li X.,CAS Tianjin Institute of Biomedical Engineering | Liu L.,CAS Tianjin Institute of Biomedical Engineering | Zhang Q.,CAS Tianjin Institute of Biomedical Engineering
Nanoscale Research Letters | Year: 2013

Oral chemotherapy is a key step towards 'chemotherapy at home', a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-α- tocopheryl polyethylene glycol 1000 succinate (PLA-PCL-TPGS) random copolymer were prepared in this research for oral delivery of antitumor agents, including thiolated chitosan-modified PCL nanoparticles, unmodified PLA-PCL-TPGS nanoparticles, and thiolated chitosan-modified PLA-PCL-TPGS nanoparticles. Firstly, the PLA-PCL-TPGS random copolymer was synthesized and characterized. Thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The PLA-PCL-TPGS nanoparticles were found by FESEM that they are of spherical shape and around 200 nm in diameter. The surface charge of PLA-PCL-TPGS nanoparticles was reversed from anionic to cationic after thiolated chitosan modification. The thiolated chitosan-modified PLA-PCL-TPGS nanoparticles have significantly higher level of the cell uptake than that of thiolated chitosan-modified PLGA nanoparticles and unmodified PLA-PCL-TPGS nanoparticles. In vitro cell viability studies showed advantages of the thiolated chitosan-modified PLA-PCL-TPGS nanoparticles over TaxolW in terms of cytotoxicity against A549 cells. It seems that the mucoadhesive nanoparticles can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein. In conclusion, PLA-PCL-TPGS nanoparticles modified by thiolated chitosan could enhance the cellular uptake and cytotoxicity, which revealed a potential application for oral chemotherapy of lung cancer. © 2013 Jiang et al.; licensee Springer.


Lv F.,CAS Tianjin Institute of Biomedical Engineering | Li Y.,CAS Tianjin Institute of Biomedical Engineering | Cao B.,CAS Tianjin Institute of Biomedical Engineering | Liu T.,CAS Tianjin Institute of Biomedical Engineering
Journal of Materials Science: Materials in Medicine | Year: 2013

Galactose substituted with zinc phthalocyanines were synthesized and characterized as near infrared fluorescent probes. The probes have good water-solubility and high emission ability in the near infrared region. With nudemice bearing liver cancer as models, in vivo fluorescence imaging effects and organ distributions of probes show that zinc phthalocyanines with three or four galactose units have good cell biocompatibility in vitro and targeting effects for liver cancer imaging in vivo. These results show the potential of these near infrared optical probes in the diagnosis of cancer in future. © 2012 Springer Science+Business Media New York.


Lv F.,CAS Tianjin Institute of Biomedical Engineering | Mao L.,CAS Tianjin Institute of Biomedical Engineering | Liu T.,CAS Tianjin Institute of Biomedical Engineering
Materials Science and Engineering C | Year: 2014

A biodegradable thermosensitive hydrogel based on four-arm PEG-PCL copolymer was prepared with porphyrin as a fluorescence tag. Its structure and composition were characterized by FTIR, 1H NMR and GPC. Sol-gel-sol transition was evaluated by the test tube-inverting method and rheological analysis. The optical properties of hydrogel were investigated by UV-vis and fluorescence spectroscopy in vitro and by fluorescence imaging system in vivo. The results show that the thermosensitive hydrogel possesses dual function of fluorescence and injectability in vivo with good biocompatibility. Consequently it can be potentially applied in biomedical field as a visible implant for in situ monitoring. © 2014 Elsevier B.V.


Wang W.,CAS Tianjin Institute of Biomedical Engineering | Song H.,CAS Tianjin Institute of Biomedical Engineering | Zhang J.,Nankai University | Li P.,CAS Tianjin Institute of Biomedical Engineering | And 4 more authors.
Journal of Controlled Release | Year: 2015

Combination chemotherapy is potent to combat diseases. Simultaneous and segregated delivery of multiple drugs in a single vehicle is essential to achieve this objective. In the present study, an injectable, thermosensitive and multicompartment hydrogel (MCH) was developed by the facile cooperative and incompatible assembly of PEGylated hydrocarbon nanoparticles with PEGylated fluorocarbon nanoparticles. The cooperative assembly behavior was investigated by fluorescence resonance energy transfer (FRET) technology, and the result demonstrated that the incompatible nanoparticle cores possibly accounted for the multicompartment formation in hydrogel. Paclitaxel and doxorubicin could be easily and separately integrated into the different compartments of MCH serving as a sustained drug cocktail formulation. In vitro drug release indicated drugs were liberated in a simultaneous but independent manner without any effect on each other. In vitro and in vivo antitumor activity indicated that peritumoral injection of drug cocktail encapsulated MCH formulation could well achieve the combination effect, which significantly improved the tumor growth inhibition efficiency as well as minimized the drug-associated side effects compared to intravenous injection of free drug cocktail. Furthermore, such a delivery device would allow precise adjustment of drug dosage to the desired effect, achieve spatial-temporal simultaneous and synchronized presence of combination drugs in the target tissue and obviate repeated drug administrations to improve patient compliance. The thermosensitive multicompartment hydrogel cocktail formulation holds great promise for simultaneous and segregated delivery of multiple bioactive agents for sustained combination therapy. © 2015 Elsevier B.V.

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