The increasing pressure from consumers and policy makers to reduce the use of synthetic polymers,whose production contributes to the depletion of non-renewable resources and are usually non-biodegradable,has prompted ...The increasing pressure from consumers and policy makers to reduce the use of synthetic polymers,whose production contributes to the depletion of non-renewable resources and are usually non-biodegradable,has prompted the efforts to find suitable bio-based sources for the production of polymers.Vegetable oils have been a frequently spotted in this search because they are versatile,highly available and a low cost liquid biosource,which can be used in the synthesis of a wide plethora of different polymers and reactive monomers.Following the same idea of reducing the environmental stress,the traditional polyurethanes that are soluble in organic solvents have been targeted for replacement,particularly in applications such as adhesives and coatings,in which the solvent is released to the atmosphere increasing the air pollution.Instead,waterborne polyurethanes(WBPU),which are polyurethane dispersions(PUD)prepared in aqueous media,release benign water to the atmosphere during use as supported or self-standing films for different applications.In this brief review,the contributions to the development of WBPUs based on vegetable oils are discussed,focusing mainly on the contributions of the last decade.The synthesis of ionic and nonionic PUDs,their characterization and the properties of the resulting dried materials,as well as derived composite materials are considered.展开更多
Waterborne polyurethane ( WBPU ) with controlled biodegradability and biocompatibility was synthesized by using poly (ε-caprolactone) ( PCL ) as the polyglycol, isophorone diisocyanate (IPDI) as the isocyanat...Waterborne polyurethane ( WBPU ) with controlled biodegradability and biocompatibility was synthesized by using poly (ε-caprolactone) ( PCL ) as the polyglycol, isophorone diisocyanate (IPDI) as the isocyanate, 2 acid (DMPA) as the chain extender and 1, 4-butanediol (BDO) as the hard-segment regulating agent. We found that BDO content significantly influenced mechanical properties, degradable performances and cyto-biocompatibility of PCL-WBPUs. Increasing the BDO content in PCL-WBPU enhanced its tensile strength and decreases strain. Enzymolysis and hydrolysis properties were also regulated by BDO content, but with different meechanisms. Cyto- biocompatibility was evaluated with ATDC5 cells. The results show that the biodegradability of PCL-WBPU is significantly determined by BDO content, which exerts a serious influence on its polymer structure, leading to resultant degradable properties.展开更多
Improvement of the treatment for Glioblastoma multiforme(GBM)especially the development of in situ controllable drug release is still a major concern.In this study,we developed waterborne biodegradable polyurethane(WB...Improvement of the treatment for Glioblastoma multiforme(GBM)especially the development of in situ controllable drug release is still a major concern.In this study,we developed waterborne biodegradable polyurethane(WBPU)scaffolds incorporated with redox-sensitive and RGD-decorated paclitaxel(PTX)polymer-drug conjugates(PDCs)for targeted GBM therapy in situ.The drug scaffolds could be implanted at residual GBM site post-operation.Dual-targeting PTX-PDCs were obtained through step-by-step conjugation of disulfide linked PTX,poly(ethylene glycol)(PEG),and arginine-glycine-aspartic acid(RGD).The RGD-modified PTX-PDCs were spherical nanoparticles(NPs)that would be released from scaffolds and identified GBM cells actively.Internalized redox-sensitive PTX-PDCs would be decomposed and release PTX inside GBM cells under the circumstances of glutathione(GSH).The release profiles of PTX from the scaffolds with/without GSH were investigated.In vitro cytotoxicity assay revealed that the dual-targeting PTX-PDCs from scaffolds could specifically kill GBM cells and protect normal cells,suggesting that dual-targeting PTX-PDC-loaded scaffolds may have the potential to repair tumor-induced brain injury.In vivo anti-recurrence assay indicated that the PTX-PDC-scaffolds could deliver PTX-PDCs to the GBM cells followed by inhibiting tumor growth and inducing apoptosis.In general,the PTX prodrug-loaded devices exhibited significant anti-GBM effects and normal tissue protection simultaneously,indicating that the WBPU scaffolds incorporated with dual-targeting PTX-PDCs may be a promising strategy for local therapy of GBM.展开更多
Lung cancer is the leading cause of cancer mortality worldwide.Preclinical studies in lung cancer hold the promise of screening for effective antitumor agents,but mechanistic studies and drug discovery based on 2D cel...Lung cancer is the leading cause of cancer mortality worldwide.Preclinical studies in lung cancer hold the promise of screening for effective antitumor agents,but mechanistic studies and drug discovery based on 2D cell models have a high failure rate in getting to the clinic.Thus,there is an urgent need to explore more reliable and effective in vitro lung cancer models.Here,we prepared a series of three-dimensional(3D)waterborne biodegradable polyurethane(WBPU)scaffolds as substrates to establish biomimetic tumor models in vitro.These 3D WBPU scaffolds were porous and could absorb large amounts of free water,facilitating the exchange of substances(nutrients and metabolic waste)and cell growth.The scaffolds at wet state could simulate the mechanics(elastic modulus∼1.9 kPa)and morphology(porous structures)of lung tissue and exhibit good biocompatibility.A549 lung cancer cells showed adherent growth pattern and rapidly formed 3D spheroids on WBPU scaffolds.Our results showed that the scaffold-based 3D lung cancer model promoted the expression of anti-apoptotic and epithelial-mesenchymal transition-related genes,giving it a more moderate growth and adhesion pattern compared to 2D cells.In addition,WBPU scaffold-established 3D lung cancer model revealed a closer expression of proteins to in vivo tumor,including tumor stem cell markers,cell proliferation,apoptosis,invasion and tumor resistance proteins.Based on these features,we further demonstrated that the 3D lung cancer model established by the WBPU scaffold was very similar to the in vivo tumor in terms of both resistance and tolerance to nanoparticulate drugs.Taken together,WBPU scaffold-based lung cancer model could better mimic the growth,microenvironment and drug response of tumor in vivo.This emerging 3D culture system holds promise to shorten the formulation cycle of individualized treatments and reduce the use of animals while providing valid research data for clinical trials.展开更多
基金the Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET,Argentina)(PIP 20170100677)the Fondo para la Investigación Científica y Tecnológica(FONCYT)(PICT-2017-1318)the Universidad Nacional de Mar del Plata(UNMdP,15/G557,ING561/19)and to the Comisión de Investigaciones Científicas de la Provincia de Buenos Aires(CIC)and the Universidad Tecnológica Nacional(UTN)for their financial support.
文摘The increasing pressure from consumers and policy makers to reduce the use of synthetic polymers,whose production contributes to the depletion of non-renewable resources and are usually non-biodegradable,has prompted the efforts to find suitable bio-based sources for the production of polymers.Vegetable oils have been a frequently spotted in this search because they are versatile,highly available and a low cost liquid biosource,which can be used in the synthesis of a wide plethora of different polymers and reactive monomers.Following the same idea of reducing the environmental stress,the traditional polyurethanes that are soluble in organic solvents have been targeted for replacement,particularly in applications such as adhesives and coatings,in which the solvent is released to the atmosphere increasing the air pollution.Instead,waterborne polyurethanes(WBPU),which are polyurethane dispersions(PUD)prepared in aqueous media,release benign water to the atmosphere during use as supported or self-standing films for different applications.In this brief review,the contributions to the development of WBPUs based on vegetable oils are discussed,focusing mainly on the contributions of the last decade.The synthesis of ionic and nonionic PUDs,their characterization and the properties of the resulting dried materials,as well as derived composite materials are considered.
基金National Natural Science Foundation of China(No.51173144)International Science&Technology Cooperation Program Supported by Ministry of Science and Technology of China and Shaanxi Province,China(No.2013KW14-02)+3 种基金Program for the Key Science and Technology Innovative Team of Shaanxi Province,China(No.2013KCT-05)China Postdoctoral Science Foundation(No.2014M562405)Natural Science Foundation of Shaanxi Province,China(No.2015JQ5137)Collaborative Innovation Center of Suzhou Nano Science and Technology,Suzhou Research Institute,China(No.BY2013036)
文摘Waterborne polyurethane ( WBPU ) with controlled biodegradability and biocompatibility was synthesized by using poly (ε-caprolactone) ( PCL ) as the polyglycol, isophorone diisocyanate (IPDI) as the isocyanate, 2 acid (DMPA) as the chain extender and 1, 4-butanediol (BDO) as the hard-segment regulating agent. We found that BDO content significantly influenced mechanical properties, degradable performances and cyto-biocompatibility of PCL-WBPUs. Increasing the BDO content in PCL-WBPU enhanced its tensile strength and decreases strain. Enzymolysis and hydrolysis properties were also regulated by BDO content, but with different meechanisms. Cyto- biocompatibility was evaluated with ATDC5 cells. The results show that the biodegradability of PCL-WBPU is significantly determined by BDO content, which exerts a serious influence on its polymer structure, leading to resultant degradable properties.
基金financially supported by Key Program of National Natural Science Foundation of China (No. 51733005)General Program of the National Natural Science Foundation of China (No. 51873122)+2 种基金National Natural Science Foundation for Young Scholars (No. 81902549)Key research and development project of science and technology department of Sichuan Province (No. 2021YFS0202)Postdoctoral Research Fund of West China Hospital (No. 2019HXBH056)
文摘Improvement of the treatment for Glioblastoma multiforme(GBM)especially the development of in situ controllable drug release is still a major concern.In this study,we developed waterborne biodegradable polyurethane(WBPU)scaffolds incorporated with redox-sensitive and RGD-decorated paclitaxel(PTX)polymer-drug conjugates(PDCs)for targeted GBM therapy in situ.The drug scaffolds could be implanted at residual GBM site post-operation.Dual-targeting PTX-PDCs were obtained through step-by-step conjugation of disulfide linked PTX,poly(ethylene glycol)(PEG),and arginine-glycine-aspartic acid(RGD).The RGD-modified PTX-PDCs were spherical nanoparticles(NPs)that would be released from scaffolds and identified GBM cells actively.Internalized redox-sensitive PTX-PDCs would be decomposed and release PTX inside GBM cells under the circumstances of glutathione(GSH).The release profiles of PTX from the scaffolds with/without GSH were investigated.In vitro cytotoxicity assay revealed that the dual-targeting PTX-PDCs from scaffolds could specifically kill GBM cells and protect normal cells,suggesting that dual-targeting PTX-PDC-loaded scaffolds may have the potential to repair tumor-induced brain injury.In vivo anti-recurrence assay indicated that the PTX-PDC-scaffolds could deliver PTX-PDCs to the GBM cells followed by inhibiting tumor growth and inducing apoptosis.In general,the PTX prodrug-loaded devices exhibited significant anti-GBM effects and normal tissue protection simultaneously,indicating that the WBPU scaffolds incorporated with dual-targeting PTX-PDCs may be a promising strategy for local therapy of GBM.
基金supported by the National Natural Science Foundation for Young Scholars(grant No.81902549)the Key research and development project of science and technology department of Sichuan Province(grant No.2021YFS0202,2021YFS0229)the Postdoctoral Research Fund of West China Hospital(grant No.2019HXBH056,2020HXBH066).
文摘Lung cancer is the leading cause of cancer mortality worldwide.Preclinical studies in lung cancer hold the promise of screening for effective antitumor agents,but mechanistic studies and drug discovery based on 2D cell models have a high failure rate in getting to the clinic.Thus,there is an urgent need to explore more reliable and effective in vitro lung cancer models.Here,we prepared a series of three-dimensional(3D)waterborne biodegradable polyurethane(WBPU)scaffolds as substrates to establish biomimetic tumor models in vitro.These 3D WBPU scaffolds were porous and could absorb large amounts of free water,facilitating the exchange of substances(nutrients and metabolic waste)and cell growth.The scaffolds at wet state could simulate the mechanics(elastic modulus∼1.9 kPa)and morphology(porous structures)of lung tissue and exhibit good biocompatibility.A549 lung cancer cells showed adherent growth pattern and rapidly formed 3D spheroids on WBPU scaffolds.Our results showed that the scaffold-based 3D lung cancer model promoted the expression of anti-apoptotic and epithelial-mesenchymal transition-related genes,giving it a more moderate growth and adhesion pattern compared to 2D cells.In addition,WBPU scaffold-established 3D lung cancer model revealed a closer expression of proteins to in vivo tumor,including tumor stem cell markers,cell proliferation,apoptosis,invasion and tumor resistance proteins.Based on these features,we further demonstrated that the 3D lung cancer model established by the WBPU scaffold was very similar to the in vivo tumor in terms of both resistance and tolerance to nanoparticulate drugs.Taken together,WBPU scaffold-based lung cancer model could better mimic the growth,microenvironment and drug response of tumor in vivo.This emerging 3D culture system holds promise to shorten the formulation cycle of individualized treatments and reduce the use of animals while providing valid research data for clinical trials.