Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications.Herein,we report the rational design and ...Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications.Herein,we report the rational design and synthesis of water-soluble keratins using a simple methodology named the QTY code.In vitro biophysical analyses and molecular dynamic simulation demonstrated a 200-fold increase in the water solubility of QTY variant keratins without apparent structural changes compared to native proteins.Homotypic self-assembly was observed for the first time in recombinant keratins in an aqueous environment,without urea and after QTY modification.Cell and animal experiments showed the in situ gel-forming capability of QTY variant keratins with superior hemostatic and wound healing activities at the wound sites compared to native recombinant keratins.Our work not only presented a simple and feasible pathway to produce large amounts of water-soluble keratins using QTY modification but also validated the enhanced self-assembly,hemostasis,and wound healing properties of these novel keratin species that may open up new venues for biomedical applications.展开更多
The aim of this research was to evaluate doxorubicin(DOX)-loaded zein in situ gels,a new drug delivery system in which a liquid state drug can be transformed into semi-solid after intratumoral injection.In vitro relea...The aim of this research was to evaluate doxorubicin(DOX)-loaded zein in situ gels,a new drug delivery system in which a liquid state drug can be transformed into semi-solid after intratumoral injection.In vitro release of DOX-loaded zein was investigated and the pharmacokinetics,biodistribution and therapeutic efficacy of these DOX-loaded zein formulations were investigated using BAI B/c nude tumor-bearing mice.In vitro release of DOX from the gels extended up to 7 days.Efficient accumulation of DOX in the tumor with lower drug concentration in blood and normal organs was obtained resulting in effective inhibition of tumor growth and fewer off-target side effects.In conclusion,a DOX-loaded in situ gel was developed with sustained release,enhanced anti-cancer efficacy for colorectal cancer in vivo,and especially with reduced off-target side effects.展开更多
基金National Natural Science Foundation of China,Grant/Award Numbers:11972099,82202340Venture&Innovation Support Program for Chongqing Overseas Returnees,Grant/Award Number:cx2020079Scientific and Fundamental Research Funds for the Central Universities,Grant/Award Numbers:2023CDJXY-050,2023CDJXY-051。
文摘Recombinant keratins possess strong hemostatic and wound healing properties but suffer from poor water solubility that restricts their bioactivities in biomedical applications.Herein,we report the rational design and synthesis of water-soluble keratins using a simple methodology named the QTY code.In vitro biophysical analyses and molecular dynamic simulation demonstrated a 200-fold increase in the water solubility of QTY variant keratins without apparent structural changes compared to native proteins.Homotypic self-assembly was observed for the first time in recombinant keratins in an aqueous environment,without urea and after QTY modification.Cell and animal experiments showed the in situ gel-forming capability of QTY variant keratins with superior hemostatic and wound healing activities at the wound sites compared to native recombinant keratins.Our work not only presented a simple and feasible pathway to produce large amounts of water-soluble keratins using QTY modification but also validated the enhanced self-assembly,hemostasis,and wound healing properties of these novel keratin species that may open up new venues for biomedical applications.
基金This study was supported by the Natural Science Foundation of China(30801444)the Natural Science Foundation of Hebei Province(H2012208020)the Hebei University of Science and Technology Discipline Construction Office and the State Key Laboratory Breeding Base-Hebei Key Laboratory of Molecular Chemistry For Drug。
文摘The aim of this research was to evaluate doxorubicin(DOX)-loaded zein in situ gels,a new drug delivery system in which a liquid state drug can be transformed into semi-solid after intratumoral injection.In vitro release of DOX-loaded zein was investigated and the pharmacokinetics,biodistribution and therapeutic efficacy of these DOX-loaded zein formulations were investigated using BAI B/c nude tumor-bearing mice.In vitro release of DOX from the gels extended up to 7 days.Efficient accumulation of DOX in the tumor with lower drug concentration in blood and normal organs was obtained resulting in effective inhibition of tumor growth and fewer off-target side effects.In conclusion,a DOX-loaded in situ gel was developed with sustained release,enhanced anti-cancer efficacy for colorectal cancer in vivo,and especially with reduced off-target side effects.
