DNA nanotechnology has been widely employed for biomedical applications.However,most DNA nanomaterials rely on noncovalent complementary base pairing of short single-stranded DNA oligonucleotides.Herein,we describe a ...DNA nanotechnology has been widely employed for biomedical applications.However,most DNA nanomaterials rely on noncovalent complementary base pairing of short single-stranded DNA oligonucleotides.Herein,we describe a general strategy to construct a long and covalently conjugated branched DNA structure for fast and in situ gelation in vivo.In our design,a short and covalently conjugated branched DNA structure can normally be employed as the DNA primer in the terminal deoxynucleotidyl transferase-dependent enzymatic polymerization system.After enzymatic extension,the DNA aptamer-modified branched DNA structures with the sequences of poly T or poly A can immediately coassemble for in situ encapsulation of the target protein and tumor cell.The fast and in situ gelation system can function in a murine model of local tumor recurrence for targeting residual tumor cells to achieve long-term drug release for efficient tumor inhibition in vivo.This rationally developed DNA self-assembly strategy provides a new avenue for the development of multifunctional DNA nanomaterials.展开更多
A glutathione-disulfide-ended poly(ethylene glycol)(GSSG-PEG-GSSG) was designed. It is a much more efficient accelerator than glutathione disulfide(GSSG) for the gelation of an 8arm-PEG-SH polymer solution, and ...A glutathione-disulfide-ended poly(ethylene glycol)(GSSG-PEG-GSSG) was designed. It is a much more efficient accelerator than glutathione disulfide(GSSG) for the gelation of an 8arm-PEG-SH polymer solution, and the gelation time can be tuned from hours to minutes at the physiological p H and temperature. A mechanism was proposed to explain the different behaviors of the GSSG and GSSG-PEG-GSSG gelation systems. Due to the ever-going thiol-disulfide exchange reaction, the thiol-disulfide hydrogels also showed interesting swelling behavior.展开更多
基金the National Key R&D Program of China(grant nos.2021YFA1200302 and 2018YFA0208900)the National Natural Science Foundation of China(grant nos.22025201,22077023,and 21721002)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(grant no.XDB36000000)the CAS Project for Young Scientists in Basic Research(grant no.YSBR-036)CAS Interdisciplinary Innovation Team,the Youth Innovation Promotion Association CAS,and the K.C.Wong Education Foundation(grant no.GJTD-2018-03).
文摘DNA nanotechnology has been widely employed for biomedical applications.However,most DNA nanomaterials rely on noncovalent complementary base pairing of short single-stranded DNA oligonucleotides.Herein,we describe a general strategy to construct a long and covalently conjugated branched DNA structure for fast and in situ gelation in vivo.In our design,a short and covalently conjugated branched DNA structure can normally be employed as the DNA primer in the terminal deoxynucleotidyl transferase-dependent enzymatic polymerization system.After enzymatic extension,the DNA aptamer-modified branched DNA structures with the sequences of poly T or poly A can immediately coassemble for in situ encapsulation of the target protein and tumor cell.The fast and in situ gelation system can function in a murine model of local tumor recurrence for targeting residual tumor cells to achieve long-term drug release for efficient tumor inhibition in vivo.This rationally developed DNA self-assembly strategy provides a new avenue for the development of multifunctional DNA nanomaterials.
基金financially supported by the National Natural Science Foundation of China(No.21004038)
文摘A glutathione-disulfide-ended poly(ethylene glycol)(GSSG-PEG-GSSG) was designed. It is a much more efficient accelerator than glutathione disulfide(GSSG) for the gelation of an 8arm-PEG-SH polymer solution, and the gelation time can be tuned from hours to minutes at the physiological p H and temperature. A mechanism was proposed to explain the different behaviors of the GSSG and GSSG-PEG-GSSG gelation systems. Due to the ever-going thiol-disulfide exchange reaction, the thiol-disulfide hydrogels also showed interesting swelling behavior.