pH-and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly(PISA). First, reversible addition-fragmentation chain transfer(RAFT) polymerizatio...pH-and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly(PISA). First, reversible addition-fragmentation chain transfer(RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate(DIPEMA) and camptothecin prodrug monomer(CPTM) using biocompatible poly(N-(2-hydroxypropyl) methacrylamide)(PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P(DIPEMA-co-CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate(Bz MA) using the PHPMA-P(DIPEMA-co-CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell(PHPMA), the drug-conjugated middle layer(P(DIPEMA-co-CPTM)) and the PBz MA core, and relatively high concentration(250 mg/g). The prodrug nanoparticles can respond to two stimuli(reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin(CPT) within the prodrug nanoparticles could be effectively triggered. p H-Induced hydrophobic/hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity.展开更多
In this study,sodium alginate(SA),a non-toxic natural polysaccharide with good biocompatibility and biodegradability,was developed for targeted delivery of curcumin(CUR)in tumor therapy.The strategy is to sulfhydrylat...In this study,sodium alginate(SA),a non-toxic natural polysaccharide with good biocompatibility and biodegradability,was developed for targeted delivery of curcumin(CUR)in tumor therapy.The strategy is to sulfhydrylate the folic acid(FA)modified SA,and the CUR dissolved in ethyl acetate(EAC)phase is coated in microcapsules by a quick,efficient and environment-friendly sonochemical method.The EAC in the microcapsule core is volatile,which can be recycled and reused to reduce cost.The prepared mi-crocapsules(FA-RSMCs@CUR)exhibited similar toxicity to free curcumin in anti-tumour evaluation in vitro.FA-RSMCs@CUR also exhibited effective antibacterial properties in the antibacterial evaluation in vitro.It is expected to become a low-cost tumor targeting vector in the future,and has the potential to be promoted in clinical application.展开更多
基金supported by the National Key R&D Program of China (2017YFA0205601)the National Natural Science Foundation of China (51625305, 21704095, 21774113, 21525420)
文摘pH-and reductive-responsive prodrug nanoparticles are constructed via a highly efficient strategy, polymerization-induced selfassembly(PISA). First, reversible addition-fragmentation chain transfer(RAFT) polymerization of 2-(diisopropylamino) ethyl methacrylate(DIPEMA) and camptothecin prodrug monomer(CPTM) using biocompatible poly(N-(2-hydroxypropyl) methacrylamide)(PHPMA-CPDB) as the macro RAFT agent is carried out, forming prodrug diblock copolymer PHPMA-P(DIPEMA-co-CPTM). Then, simultaneous fulfillment of polymerization, self-assembly, and drug encapsulation are achieved via RAFT dispersion polymerization of benzyl methacrylate(Bz MA) using the PHPMA-P(DIPEMA-co-CPTM) as the macro RAFT agent. The prodrug nanoparticles have three layers, the biocompatible shell(PHPMA), the drug-conjugated middle layer(P(DIPEMA-co-CPTM)) and the PBz MA core, and relatively high concentration(250 mg/g). The prodrug nanoparticles can respond to two stimuli(reductive and acidic conditions). Due to reductive microenvironment of cytosol, the cleavage of the conjugated camptothecin(CPT) within the prodrug nanoparticles could be effectively triggered. p H-Induced hydrophobic/hydrophilic transition of the PDIPEMA chains results in faster diffusion of GSH into the CPTM units, thus accelerated release of CPT is observed in mild acidic and reductive conditions. Cell viability assays show that the prodrug nanoparticles exhibit well performance of intracellular drug delivery and good anticancer activity.
基金supported by the Pharmaceutical Health Industry Development Special Project of the Science and Technology Department of Jilin Province,China(grant No.20210401172YY)Interdisciplinary Research Funding Program for Doctoral Students of jilin University(grant No.101832020DjX026).
文摘In this study,sodium alginate(SA),a non-toxic natural polysaccharide with good biocompatibility and biodegradability,was developed for targeted delivery of curcumin(CUR)in tumor therapy.The strategy is to sulfhydrylate the folic acid(FA)modified SA,and the CUR dissolved in ethyl acetate(EAC)phase is coated in microcapsules by a quick,efficient and environment-friendly sonochemical method.The EAC in the microcapsule core is volatile,which can be recycled and reused to reduce cost.The prepared mi-crocapsules(FA-RSMCs@CUR)exhibited similar toxicity to free curcumin in anti-tumour evaluation in vitro.FA-RSMCs@CUR also exhibited effective antibacterial properties in the antibacterial evaluation in vitro.It is expected to become a low-cost tumor targeting vector in the future,and has the potential to be promoted in clinical application.