Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of e...Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of efficient strategies for delivering proteins and the rapid clearance of therapeutic proteins in vivo after their administration. Here, we demonstrate a novel strategy that can significantly prolong the circulation time of therapeutic proteins as well as minimize their immunogenicity. This is achieved by encapsulating individual protein molecules with a thin layer of crosslinked phosphorylcholine polymer that resists protein adsorption. Through extensive cellular studies, we demonstrate that the crosslinked phosphorylcholine polymer shell effectively prevents the encapsulated protein from being phagocytosed by macrophages, which play an essential role in the clearance of nanoparfides in vivo. Moreover, the polymer shell prevents the encapsulated protein from being identified by immune cells. As a result, immune responses against the therapeutic protein are effectively suppressed. This work describes a feasible method to prolong the circulation time and reduce the immunogenicity of therapeutic proteins, which may promote the development and application of novel protein therapies in the treatment of diverse diseases.展开更多
Background: The number of people presenting with osteoarthritis is increasing due, largely, to an ageing population and advances in medical treatments. This is driving the demand for new clinical solutions and treatme...Background: The number of people presenting with osteoarthritis is increasing due, largely, to an ageing population and advances in medical treatments. This is driving the demand for new clinical solutions and treatments for the disease. Biologic therapies have been touted as an adjunct, or even alternative to established treatments for osteoarthritis. The term “biologics” refers to protein-based therapeutics that are derived from the proteins of living organisms. These treatments include, but are not limited to: autologous blood products such as platelet rich plasma (PRP), cell therapies such as autologous chondrocyte implantation (ACI) and mesenchymal stem cells, growth factors and cytokines, gene therapy. Aim: This study aims to provide a clear definition of these technologies and describe the evidence supporting their clinical efficacy to treat osteoarthritis. This is to provide clarity to both clinicians and patients on the range of technologies available. Method: Literature databases Embase and PubMed were searched for keywords such as “biologic”, “osteoarthritis”. Results: The literature identified 4 primary categories of biologic treatments for osteoarthritis: stem cell therapy, somatic cell therapy, protein therapy and gene therapy. The evidence level varied in its quality from treatment to treatment, as did the conclusions of published studies. Conclusion: Autologous chondrocyte therapy had the most convincing evidence to support its use as a treatment for osteoarthritis, however, current methods of use produced variable results. Other treatments such as platelet rich plasma and bone marrow derived stem cells show promise as potential future therapies, with more refinement, but evidence does not support their use currently. Other treatments including autologous stem cells should be avoided until there is a greater quantity and quality of evidence supporting their use.展开更多
Short in vivo circulation is a major hindrance to the widespread adoption of protein therapeutics. Protein nanocapsules generated by encapsulating proteins with a thin layer of phosphorylcholine-based polymer via a tw...Short in vivo circulation is a major hindrance to the widespread adoption of protein therapeutics. Protein nanocapsules generated by encapsulating proteins with a thin layer of phosphorylcholine-based polymer via a two-step encapsulation process exhibited significantly prolonged plasma half-life. Furthermore, by constructing nanocapsules with similar sizes but different surface charges and chemistry, we demonstrated a generic strategy for prolonging the plasma half-life of therapeutic proteins. In an in vitro experiment, four types of bovine serum albumin （BSA） nanocapsules were incubated with fetal bovine serum （FBS） in phosphate buffer saline （PBS）; the cell uptake by HeLa cells was monitored to systematically evaluate the characteristics of the surface chemistry during drculation. Single positron emission tomography-computed tomography （SPECT） was employed to allow real-time observation of the BSA nanoparticle distribution in vivo, as well as quantification of the plasma concentration after intravenous administration. This study offers a practical method for translating a broad range of proteins for clinical use.展开更多
Biopharmaceuticals, including proteins, DNAs, and RNAs, hold vast promise for the treatment of many disorders, such as cancer, diabetes, autoimmune diseases, infectious diseases, and rare diseases. The application of ...Biopharmaceuticals, including proteins, DNAs, and RNAs, hold vast promise for the treatment of many disorders, such as cancer, diabetes, autoimmune diseases, infectious diseases, and rare diseases. The application of biopharmaceuticals, however, is limited by their poor stability, immunogenicity, suboptimal pharmacokinetic performance, undesired tissue distribution, and low penetration through biological barriers. In situ polymerization provides an appealing and promising platform to improve the pharmacological characteristics of biopharmaceuticals. Instead of the traditional ＂grafting to＂ polymer-biomolecule conjugation, in situ polymerization grows polymers on the surfaces of the biomacromolecules, resulting in easier purification procedures, high conjugation yields, and unique structures. Herein, this review surveys recent advances in the polymerization methodologies. Additionally, we further review improved therapeutic performance of the resultant nanomedicines. Finally, the opportunities, as well as the challenges, of these nanocomposites in the biomedical fields are discussed.展开更多
基金This work is supported by the National Natural Science Foundation of China （NSFC, Nos. 91127045, 51390483, 51473319, 51303025, 81401439 and 51343007）, YG2012MS38 and China Postdoctoral Science Foundation （No. 2014M551399）.
文摘Protein therap34 wherein therapeutic proteins are delivered to treat disorders, is considered the safest and most direct approach for treating diseases. However, its applications are highly limited by the paucity of efficient strategies for delivering proteins and the rapid clearance of therapeutic proteins in vivo after their administration. Here, we demonstrate a novel strategy that can significantly prolong the circulation time of therapeutic proteins as well as minimize their immunogenicity. This is achieved by encapsulating individual protein molecules with a thin layer of crosslinked phosphorylcholine polymer that resists protein adsorption. Through extensive cellular studies, we demonstrate that the crosslinked phosphorylcholine polymer shell effectively prevents the encapsulated protein from being phagocytosed by macrophages, which play an essential role in the clearance of nanoparfides in vivo. Moreover, the polymer shell prevents the encapsulated protein from being identified by immune cells. As a result, immune responses against the therapeutic protein are effectively suppressed. This work describes a feasible method to prolong the circulation time and reduce the immunogenicity of therapeutic proteins, which may promote the development and application of novel protein therapies in the treatment of diverse diseases.
文摘Background: The number of people presenting with osteoarthritis is increasing due, largely, to an ageing population and advances in medical treatments. This is driving the demand for new clinical solutions and treatments for the disease. Biologic therapies have been touted as an adjunct, or even alternative to established treatments for osteoarthritis. The term “biologics” refers to protein-based therapeutics that are derived from the proteins of living organisms. These treatments include, but are not limited to: autologous blood products such as platelet rich plasma (PRP), cell therapies such as autologous chondrocyte implantation (ACI) and mesenchymal stem cells, growth factors and cytokines, gene therapy. Aim: This study aims to provide a clear definition of these technologies and describe the evidence supporting their clinical efficacy to treat osteoarthritis. This is to provide clarity to both clinicians and patients on the range of technologies available. Method: Literature databases Embase and PubMed were searched for keywords such as “biologic”, “osteoarthritis”. Results: The literature identified 4 primary categories of biologic treatments for osteoarthritis: stem cell therapy, somatic cell therapy, protein therapy and gene therapy. The evidence level varied in its quality from treatment to treatment, as did the conclusions of published studies. Conclusion: Autologous chondrocyte therapy had the most convincing evidence to support its use as a treatment for osteoarthritis, however, current methods of use produced variable results. Other treatments such as platelet rich plasma and bone marrow derived stem cells show promise as potential future therapies, with more refinement, but evidence does not support their use currently. Other treatments including autologous stem cells should be avoided until there is a greater quantity and quality of evidence supporting their use.
基金This work is supported by the National Natural Science Foundation of China （NSFC, Nos. 51343007, 81271612 and 81401439）, Shanghai Pujiang Program （No. 13PJD022）, and Shanghai Health Bureau Fund （No. 20124016）.
文摘Short in vivo circulation is a major hindrance to the widespread adoption of protein therapeutics. Protein nanocapsules generated by encapsulating proteins with a thin layer of phosphorylcholine-based polymer via a two-step encapsulation process exhibited significantly prolonged plasma half-life. Furthermore, by constructing nanocapsules with similar sizes but different surface charges and chemistry, we demonstrated a generic strategy for prolonging the plasma half-life of therapeutic proteins. In an in vitro experiment, four types of bovine serum albumin （BSA） nanocapsules were incubated with fetal bovine serum （FBS） in phosphate buffer saline （PBS）; the cell uptake by HeLa cells was monitored to systematically evaluate the characteristics of the surface chemistry during drculation. Single positron emission tomography-computed tomography （SPECT） was employed to allow real-time observation of the BSA nanoparticle distribution in vivo, as well as quantification of the plasma concentration after intravenous administration. This study offers a practical method for translating a broad range of proteins for clinical use.
文摘Biopharmaceuticals, including proteins, DNAs, and RNAs, hold vast promise for the treatment of many disorders, such as cancer, diabetes, autoimmune diseases, infectious diseases, and rare diseases. The application of biopharmaceuticals, however, is limited by their poor stability, immunogenicity, suboptimal pharmacokinetic performance, undesired tissue distribution, and low penetration through biological barriers. In situ polymerization provides an appealing and promising platform to improve the pharmacological characteristics of biopharmaceuticals. Instead of the traditional ＂grafting to＂ polymer-biomolecule conjugation, in situ polymerization grows polymers on the surfaces of the biomacromolecules, resulting in easier purification procedures, high conjugation yields, and unique structures. Herein, this review surveys recent advances in the polymerization methodologies. Additionally, we further review improved therapeutic performance of the resultant nanomedicines. Finally, the opportunities, as well as the challenges, of these nanocomposites in the biomedical fields are discussed.
