Polymerization-induced self-assembly (PISA) was used to fabricate polymeric nanoparticles via reversible ad- dition-fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) usi...Polymerization-induced self-assembly (PISA) was used to fabricate polymeric nanoparticles via reversible ad- dition-fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) using di- block copolymer poly(glycerol monomethacrytate)-block-poly(2-dimethylaminoetbyl methacrylate) (PGMMA- PDMAEMA-CTA) as the macro RAFT agent. The dispersion of polymeric nanoparticles with a final concentration of about 210 mg/g (solid content of 21%) was obtained via this efficient method (PISA). The resultant polymeric nanoparticles consisting of corona-shell-core three layers with weak polyelectrolyte PDMAEMA as the shell were used as sacrificial template to fabricate TiO2 hollow nanoparticles. The negatively charged titanium precursor was absorbed into the PDMAEMA shell via the electrostatic interaction, and hydrolyzed to form polymer/TiO2 hybrid nanoparticles. Anatase TiO2 hollow nanoparticles were formed after removing the polymeric templates by calcina- tion at 550 ℃. The experiments of photocatalytic degradation of methyl orange showed that the resultant anatase TiO2 hollow nanoparticles had high photocatalytic activity and good reusability.展开更多
Biodegradable polymeric nanoparticles are more and more frequently used in drug delivery systems, which represent one of the most rapidly developing areas. In our previous study, a novel natural hybrid polyester, poly...Biodegradable polymeric nanoparticles are more and more frequently used in drug delivery systems, which represent one of the most rapidly developing areas. In our previous study, a novel natural hybrid polyester, polyethylene glycol 200 (PEG200) end-capped poly (3-hydroxybutyrate-co-3-hydroxyhcxanoate) (PHBHHx-PEG) was directly produced by Aeromonas hydrophila fermentation. In this study, the performance of the novel biodegradable PHBHHx-PEG copolyester as a sustained release carrier for hydrophobic drugs with different molecular weights and the in vitro sustained release profile were investigated. 5-Fluorouracil (5-Fu, Mw=130.1), TGX221 (Mw=364.4), and Rapamycin (RAP, Mw=914.2) were used as the model drugs. PHBHHx-PEG nanoparticles entrapped with 5-Fu, TGX221 and RAP were fabricated by a modified emulsification/solvent evaporation method, respectively. The average diameter of 5-Fu, TGX221, and RAP loaded PHBHHx-PEG nanoparticles was between 198.2-217.4 nm, and the entrapment efficiency of the three drugs was 62.5%, 93.4% and 91.9%, respectively. The in vitro release profiles of 5-Fu, TGX221 and RAP from PHBHHx-PEG nanoparticles were different. 5-Fu showed faster release rate and an obvious initial burst release phase. TGX221 and RAP were demonstrated to be released more slowly and steadily. The release percentages of 5-Fu, TGX221 and RAP were 97.7%, 85.1% and 74.7% after releasing for 72 h. PHBHHx-PEG is a kind of promising material as a carrier for the entrapment and delivery of hydrophobic drugs especially for those drugs with high molecular weight.展开更多
Current approaches for the treatment of chronic lymphocytic leukemia (CLL) have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to r...Current approaches for the treatment of chronic lymphocytic leukemia (CLL) have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to reducing the long-term side- effects of therapeutics for all leukemia patients, there is an urgent need for novel therapeutic strategies for difficult-to-treat leukemia cases. Due to the cytotoxicity of drugs, the major challenge currently is to deliver the therapeutic agents to neoplastic cells while preserving the viability of non-malignant ceils. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanopartides coated with an anti-CD20 antibody.We first demonstrated the ability of the nanoparticles to target and internalize in tumor B-cells. Moreover, these nanoparticles could kill not only p53-mutated]deleted leukemia cells expressing a low amount of CD20, but also circulating primary ceils isolated from chronic lymphocytic leukemia patients. The safety of these nanoparticles was also demonstrated in healthy mice, and their therapeutic effects were shown in a new model of aggressive leukemia. These results showed that anti-CD20 nanoparticles containing hydroxychloroquine and chlorambucil can be effective in controlling aggressive leukemia and provided a rationale for adopting this approach for the treatment of other B-cell disorders.展开更多
基金The financial support from the National Natural Science Foundation of China (Nos. 21525420 and 21374107) and China Postdoctoral Science Foundation (BH2060000011) is gratefully acknowledged.
文摘Polymerization-induced self-assembly (PISA) was used to fabricate polymeric nanoparticles via reversible ad- dition-fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) using di- block copolymer poly(glycerol monomethacrytate)-block-poly(2-dimethylaminoetbyl methacrylate) (PGMMA- PDMAEMA-CTA) as the macro RAFT agent. The dispersion of polymeric nanoparticles with a final concentration of about 210 mg/g (solid content of 21%) was obtained via this efficient method (PISA). The resultant polymeric nanoparticles consisting of corona-shell-core three layers with weak polyelectrolyte PDMAEMA as the shell were used as sacrificial template to fabricate TiO2 hollow nanoparticles. The negatively charged titanium precursor was absorbed into the PDMAEMA shell via the electrostatic interaction, and hydrolyzed to form polymer/TiO2 hybrid nanoparticles. Anatase TiO2 hollow nanoparticles were formed after removing the polymeric templates by calcina- tion at 550 ℃. The experiments of photocatalytic degradation of methyl orange showed that the resultant anatase TiO2 hollow nanoparticles had high photocatalytic activity and good reusability.
基金National Natural Science Foundation of Chinagrant number:81172170,81371288+1 种基金Science and Technology Research and Development Program of Shanxi Provincegrant number:2013KW32-04
文摘Biodegradable polymeric nanoparticles are more and more frequently used in drug delivery systems, which represent one of the most rapidly developing areas. In our previous study, a novel natural hybrid polyester, polyethylene glycol 200 (PEG200) end-capped poly (3-hydroxybutyrate-co-3-hydroxyhcxanoate) (PHBHHx-PEG) was directly produced by Aeromonas hydrophila fermentation. In this study, the performance of the novel biodegradable PHBHHx-PEG copolyester as a sustained release carrier for hydrophobic drugs with different molecular weights and the in vitro sustained release profile were investigated. 5-Fluorouracil (5-Fu, Mw=130.1), TGX221 (Mw=364.4), and Rapamycin (RAP, Mw=914.2) were used as the model drugs. PHBHHx-PEG nanoparticles entrapped with 5-Fu, TGX221 and RAP were fabricated by a modified emulsification/solvent evaporation method, respectively. The average diameter of 5-Fu, TGX221, and RAP loaded PHBHHx-PEG nanoparticles was between 198.2-217.4 nm, and the entrapment efficiency of the three drugs was 62.5%, 93.4% and 91.9%, respectively. The in vitro release profiles of 5-Fu, TGX221 and RAP from PHBHHx-PEG nanoparticles were different. 5-Fu showed faster release rate and an obvious initial burst release phase. TGX221 and RAP were demonstrated to be released more slowly and steadily. The release percentages of 5-Fu, TGX221 and RAP were 97.7%, 85.1% and 74.7% after releasing for 72 h. PHBHHx-PEG is a kind of promising material as a carrier for the entrapment and delivery of hydrophobic drugs especially for those drugs with high molecular weight.
文摘Current approaches for the treatment of chronic lymphocytic leukemia (CLL) have greatly improved the prognosis for survival, but some patients remain refractive to these therapeutic regimens. Hence, in addition to reducing the long-term side- effects of therapeutics for all leukemia patients, there is an urgent need for novel therapeutic strategies for difficult-to-treat leukemia cases. Due to the cytotoxicity of drugs, the major challenge currently is to deliver the therapeutic agents to neoplastic cells while preserving the viability of non-malignant ceils. In this study, we propose a therapeutic approach in which high doses of hydroxychloroquine and chlorambucil were loaded into biodegradable polymeric nanopartides coated with an anti-CD20 antibody.We first demonstrated the ability of the nanoparticles to target and internalize in tumor B-cells. Moreover, these nanoparticles could kill not only p53-mutated]deleted leukemia cells expressing a low amount of CD20, but also circulating primary ceils isolated from chronic lymphocytic leukemia patients. The safety of these nanoparticles was also demonstrated in healthy mice, and their therapeutic effects were shown in a new model of aggressive leukemia. These results showed that anti-CD20 nanoparticles containing hydroxychloroquine and chlorambucil can be effective in controlling aggressive leukemia and provided a rationale for adopting this approach for the treatment of other B-cell disorders.