A scalable and versatile strategy was developed for the fabrication of uniform polymeric microspheres with controllable interconnected porous structures. Uniform water-in-oil-in-water emulsions with linear poly(methyl...A scalable and versatile strategy was developed for the fabrication of uniform polymeric microspheres with controllable interconnected porous structures. Uniform water-in-oil-in-water emulsions with linear poly(methyl methacrylate-glycidyl methacrylate) in the oil phase were generated by two-step premix membrane emulsification and used for constructing the microspheres. During the emulsion solidification process, internal water droplets were packed densely together, forming a thin oil film between the internal and external water phases. After solvent diffusion, the thin film can be ruptured and pores can be templated from the internal water droplets to form interconnected porous structures. Membranes with various pore sizes were obtained. The osmotic pressure and Laplace pressure balance were used to control the porosity and pore size precisely. The proposed method enables the fabrication of functional polymeric microspheres with uniform and controllable porous structures and particle sizes. This improves their performance and broadens the scope of their applications, especially in chromatographic separation.展开更多
Insulin entrapped nanocapsules to use polylactide （PLA） as the encapsulating material were prepared through a modified water-in-oil-in-water （W/O/W） emulsification and solvent evaporation method, The average parti...Insulin entrapped nanocapsules to use polylactide （PLA） as the encapsulating material were prepared through a modified water-in-oil-in-water （W/O/W） emulsification and solvent evaporation method, The average particle size of PLA nanocapsules obtained was decreased to （181.5 ± 8.4） nm, and capably adjusted from 180 to 370 nm by using different types and content of nonionic emulsifiers. The influence of emulsifiers on property of nanocapsules was discussed in detail. The effects of spans and tweens to modify the size of the nanocapsules were different, which can be due to the distribution of the surfactants on the inner interface between the inner water and oil of the double emulsion. The encapsulation efficiency and drug release of nanocapsules were affected obviously by the content and type of emulsifiers.展开更多
Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during c...Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.展开更多
基金the National Natural Science Foundation of China(Nos.21336010 and 81772417)the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA16021400).
文摘A scalable and versatile strategy was developed for the fabrication of uniform polymeric microspheres with controllable interconnected porous structures. Uniform water-in-oil-in-water emulsions with linear poly(methyl methacrylate-glycidyl methacrylate) in the oil phase were generated by two-step premix membrane emulsification and used for constructing the microspheres. During the emulsion solidification process, internal water droplets were packed densely together, forming a thin oil film between the internal and external water phases. After solvent diffusion, the thin film can be ruptured and pores can be templated from the internal water droplets to form interconnected porous structures. Membranes with various pore sizes were obtained. The osmotic pressure and Laplace pressure balance were used to control the porosity and pore size precisely. The proposed method enables the fabrication of functional polymeric microspheres with uniform and controllable porous structures and particle sizes. This improves their performance and broadens the scope of their applications, especially in chromatographic separation.
文摘Insulin entrapped nanocapsules to use polylactide （PLA） as the encapsulating material were prepared through a modified water-in-oil-in-water （W/O/W） emulsification and solvent evaporation method, The average particle size of PLA nanocapsules obtained was decreased to （181.5 ± 8.4） nm, and capably adjusted from 180 to 370 nm by using different types and content of nonionic emulsifiers. The influence of emulsifiers on property of nanocapsules was discussed in detail. The effects of spans and tweens to modify the size of the nanocapsules were different, which can be due to the distribution of the surfactants on the inner interface between the inner water and oil of the double emulsion. The encapsulation efficiency and drug release of nanocapsules were affected obviously by the content and type of emulsifiers.
基金partially supported by the National Natural Science Foundation of China(51802209,22077093,51761145041,51525203)the National Research Programs from Ministry of Science and Technology(MOST)of China(2016YFA0201200)+3 种基金the Natural Science Foundation of Jiangsu Province(BK20180848)the Jiangsu Social Development Project(BE2019658)Collaborative Innovation Center of Suzhou Nano Science and Technologythe 111 Program from the Ministry of Education of China.
文摘Due to the negative roles of tumor microenvironment(TME)in compromising therapeutic responses of various cancer therapies,it is expected that modulation of TME may be able to enhance the therapeutic responses during cancer treatment.Herein,we develop a concise strategy to prepare pH-responsive nanoparticles via the CaCO3-assisted double emulsion method,thereby enabling effective co-encapsulation of both doxorubicin(DOX),an immunogenic cell death(ICD)inducer,and alkylated NLG919(aNLG919),an inhibitor of indoleamine 2,3-dioxygenase 1(IDO1).The obtained DOX/aNLG919-loaded CaCO3 nanoparticles(DNCaNPs)are able to cause effective ICD of cancer cells and at the same time restrict the production of immunosuppressive kynurenine by inhibiting IDO1.Upon intravenous injection,such DNCaNPs show efficient tumor accumulation,improved tumor penetration of therapeutics and neutralization of acidic TME.As a result,those DNCaNPs can elicit effective anti-tumor immune responses featured in increased density of tumor-infiltrating CD8+cytotoxic T cells as well as depletion of immunosuppressive regulatory T cells(Tregs),thus effectively suppressing the growth of subcutaneous CT26 and orthotopic 4T1 tumors on the Balb/c mice through combined chemotherapy&immunotherapy.This study presents a compendious strategy for construction of pH-responsive nanoparticles,endowing significantly enhanced chemo-immunotherapy of cancer by overcoming the immunosuppressive TME.
