Poly-L-lysine(PLL)is a water-soluble biopolymer consist of repeating unit of L-lysine.It displays intrinsic non-antigenicity,antibacterial property,biocompatibility,and biodegradability,and facile synthesis procedure,...Poly-L-lysine(PLL)is a water-soluble biopolymer consist of repeating unit of L-lysine.It displays intrinsic non-antigenicity,antibacterial property,biocompatibility,and biodegradability,and facile synthesis procedure,there-fore has attracted particular attention in various biomedical and pharmaceutical applications.Following a brief introduction to PLL synthesis,this review focuses on the significant advances of PLL and PLL-derived complexes utilized in cargo delivery,tissue adhesives,and antibacterial materials.Meanwhile,this review summarized the modification and optimization of PLL complexes for further clinical translational studies.The final section dis-cusses the challenges and opportunities of PLL-based complexes in the biomedical areas.展开更多
Commercial tissue adhesives have been widely applied in wound hemostats and dressings while enhancing the hemostasis and healing capabilities is challenging to meet clinical needs.Herein,we designed the glucose-and ca...Commercial tissue adhesives have been widely applied in wound hemostats and dressings while enhancing the hemostasis and healing capabilities is challenging to meet clinical needs.Herein,we designed the glucose-and catechol-functionalized derivatives from commercialε-polylysine(EPL)and prepared the hydrogels by simple amidation and catechol-crosslinking reactions,which have larger swelling ratios of 220%–240%,suitable microporous size of about 6–8µm,and tissue adhesion strength of about 20–40 kPa.The hemolysis,cytotoxicity,and cellular double-staining assays indicate that those hydrogels had good biocompatibility and the H-3 hydrogel with higher glucose content gave a lower hemolysis ratio of 0.73%±0.14%.The blood-clotting index,blood cell attachment and adhesion studies showed those hydrogels had fast blood-coagulation,resulting in excellent hemostasis performance with a short hemostatic time of 38–46 s and less blood loss of 19%–34%in a liver hemorrhage model.A full-thickness rat-skin defect model further demonstrates that the H-3 hydrogel achieved fast wound healing with a wound closure of 70.0%±2.7%on postoperative day 7 and nearly full closure on day 14.Remarkably,the hydroproline level that denotes the collagen production reached a higher one of 7.24±0.55µg/mg comparable to that in normal skins on day 14,evidencing the wound healing was close to completion in the H-3 treatment.Consequently,this work provides a simple method to construct a glycosylated and catechol-functionalized hydrogel platform from commercial EPL,holding translational potentials in wound hemostats and dressings.展开更多
Polyethylenimine-poly(L-lysine) (PEI-PLL) copolymer was synthesized via ring-opening polymerization of L-lysine N-carboxyanhydride (Lys(Z)-NCA) initiated by PEI. The complexation of PEI-PLL with siRNA was stud...Polyethylenimine-poly(L-lysine) (PEI-PLL) copolymer was synthesized via ring-opening polymerization of L-lysine N-carboxyanhydride (Lys(Z)-NCA) initiated by PEI. The complexation of PEI-PLL with siRNA was studied by particle size and zeta potential measurements. The flow cytometric analysis and confocal imaging showed its excellent intracellular trafficking ability. PEI-PLL displayed higher gene silencing efficiency and lower cytotoxicity than commercial PEI-25k in vitro. In the antitumor study, PEI-PLL was further combined with siVEGF and showed obviously tumor inhibition effect for the treatment of CT26 tumor model. Therefore, PEI-PLL is a promising siRNA carrier candidate for further antitumor treatment in vivo.展开更多
Cell transplantation is an effective strategy to improve the repair effect of nerve guide conduits(NGCs).However,problems such as low loading efficiency and cell anoikis undermine the outcomes.Microcarriers are effici...Cell transplantation is an effective strategy to improve the repair effect of nerve guide conduits(NGCs).However,problems such as low loading efficiency and cell anoikis undermine the outcomes.Microcarriers are efficient 3D cell culture scaffolds,which can also prevent cell anoikis by providing substrate for adhesion during transplantation.Here,we demonstrate for the first time microcarrier-based cell transplantation in peripheral nerve repair.We first prepared macroporous chitosan microcarriers(CSMCs)by the emulsion-phase separation method,and then decorated the CSMCs with polylysine(pl-CSMCs)to improve cell affinity.We then loaded the pl-CSMCs with adipose-derived stem cells(ADSCs)and injected them into electrospun polycaprolactone/chitosan NGCs to repair rat sciatic nerve defects.The ADSCs-laden pl-CSMCs effectively improved nerve regeneration as demonstrated by evaluation of histology,motor function recovery,electrophysiology,and gastrocnemius recovery.With efficient cell transplantation,convenient operation,and the multiple merits of ADSCs,the ADSCs-laden pl-CSMCs hold good potential in peripheral nerve repair.展开更多
Chirality is a key factor in the biological activity of many biomolecules. Poly(L-lysine)(PLL), a polypeptide synthesized from L-lysine, is one of the mostly used cationic polymers for gene delivery. The effect of...Chirality is a key factor in the biological activity of many biomolecules. Poly(L-lysine)(PLL), a polypeptide synthesized from L-lysine, is one of the mostly used cationic polymers for gene delivery. The effect of chirality of polylysine(PL) on its gene delivery remains unknown. Herein, we prepared three polylysines(PLs) with the similar molecular weight but different backbone chiralities including poly(L-lysine)(PLL), poly(D-lysine)(PDL) and poly(DL-lysine)(PDLL). The side chains of each PL were modified with propylene oxide(PO) of different chiralities including(R)PO,(S)PO and(R,S)PO. These PL-POs with distinct chirality in main and side chains could condense p DNA into polyplexes. The polyplexes had approximately the same size, zeta potential and binding ability, but showed distinct gene transfection efficiency. We found that the PLs of L-configuration in the main chain had higher transfection efficiency than that of D or DL configuration due to their faster cellular uptake, while the side chain chirality had no effect on transfection efficiency.展开更多
The ring-opening polymerization (ROP) of N-(tetrafluoroboran ammonium)-L-lysine-N-carboxyanhydride (NH3BF4-Lys NCA) was initiated by triethylamine to prepare hyperbranched polylysine (HPlys) fluoroborate with narrow p...The ring-opening polymerization (ROP) of N-(tetrafluoroboran ammonium)-L-lysine-N-carboxyanhydride (NH3BF4-Lys NCA) was initiated by triethylamine to prepare hyperbranched polylysine (HPlys) fluoroborate with narrow polydispersity at a low temperature. Both mass spectroscopy analysis and DFT computation evidenced that the resultant cyclic dimer mainly initiated ROP as a secondary species according to normal amine mechanism. The hyperbranched polylysine in aqueous solution existed in a unimolecular state at low concentrations, but transformed into spherical micellar aggregates at a high concentration of 5 mg/mL, as characterized by dynamic laser scattering and transmission electron microscopy. By utilizing multivalent coordination interactions between hyperbranched polylysine and gold, the plasmonic gold nanoparticles (HPlys@Au NPs) were successfully prepared in aqueous solution, which elevated the solution by 23.1℃ upon 5 min of NIR laser irradiation (808 nm, 2 W/cm2).展开更多
DTPA was covalently conjugated to the copolymer of L-lysine and L-tyrosine,then transchelated with Gd-EDTA,the resultant polymer chelates were further reacted with 6-O-bromoacetyl-D-galactose or methyl lactobionyloxya...DTPA was covalently conjugated to the copolymer of L-lysine and L-tyrosine,then transchelated with Gd-EDTA,the resultant polymer chelates were further reacted with 6-O-bromoacetyl-D-galactose or methyl lactobionyloxyacetate to give PLT(Gd-DTPA)with galactose moiety as liver-targeting group.These macromolecular MRI contrast agents were characterized by means of FT-IR,ICP-AES,elementary analyses and UV-Vis spectrophotometry.Their in vitro relaxivity and liver targeting property in mice were also investigated.展开更多
Oligo-(lysine) n (n = 1-4) containing different numbers of lysine residues was used to induce the condensation of silicic acid to form silica particles in neutral silicate solution. It was found that the condensat...Oligo-(lysine) n (n = 1-4) containing different numbers of lysine residues was used to induce the condensation of silicic acid to form silica particles in neutral silicate solution. It was found that the condensation rate and the formation of silica particles are dependent on the number of lysine residues in an oligo-lysine. Oligo-lysine with more lysine residues can link more silicic acid together to form a matrix that promotes the effective aggregation of the condensed silica pieces to form large silica particles.展开更多
It was found that microperoxidase-11 (MP-if) can undergo photoreduction at the bareroughened silver electrode. No photoreduction happens at the roughened silver electrodemodified with mercaptoundecanoic carboxylic aci...It was found that microperoxidase-11 (MP-if) can undergo photoreduction at the bareroughened silver electrode. No photoreduction happens at the roughened silver electrodemodified with mercaptoundecanoic carboxylic acid/poly-lysine. The photoreduction mechanismis discussed.展开更多
Medical devices-related infections pose a great threat to patients and cause an increased morbidity and mortality. Herein, we prepare an antibacterial composite(TPU-x) through blending medical grade thermoplastic poly...Medical devices-related infections pose a great threat to patients and cause an increased morbidity and mortality. Herein, we prepare an antibacterial composite(TPU-x) through blending medical grade thermoplastic polyurethane(TPU) and the complex(PL-DOSS) of ε-polylysine(ε-PL) and docusate sodium(DOSS). >99% reduction of colony forming unit(CFU) can be obtained in TPU-x composite films even at relatively low content of PL-DOSS, e.g. 0.13% for Methicillin resistant S. aureus(MRSA) and 0.5% for E. coli. The excellent antibacterial activity is mainly attributed to the formation of PL-DOSS nanoparticles that are uniformly dispersed in the TPU matrix with a size of ~100 nm. TPU-x composite films exhibit long-term stability in saline and good biocompatibility, and retain mechanical properties of TPU.展开更多
基金supported by the Natural Science Foundation of Jiangsu Province (BK20210016)the National Key R&D Program of China (2020YFA0710800)+2 种基金the Key Program of National Natural Science Foundation of China (grant no.81930043)the Major International (Regional)Joint Research Project of China (grant no.81720108020)the Jiangsu Provincial Key Research and Development Program (BE2020621).
文摘Poly-L-lysine(PLL)is a water-soluble biopolymer consist of repeating unit of L-lysine.It displays intrinsic non-antigenicity,antibacterial property,biocompatibility,and biodegradability,and facile synthesis procedure,there-fore has attracted particular attention in various biomedical and pharmaceutical applications.Following a brief introduction to PLL synthesis,this review focuses on the significant advances of PLL and PLL-derived complexes utilized in cargo delivery,tissue adhesives,and antibacterial materials.Meanwhile,this review summarized the modification and optimization of PLL complexes for further clinical translational studies.The final section dis-cusses the challenges and opportunities of PLL-based complexes in the biomedical areas.
基金financially supported by National Key Research and Development Project of China (No. 2021YFB4001101)the National Natural Science Foundation (NSFC) of China (No.22075176)+1 种基金Natural Science Foundation of Shanghai (No.22ZR1429200)NSFC projects (Nos. 51833006, 82071160,81870806 and 81974152)
文摘Commercial tissue adhesives have been widely applied in wound hemostats and dressings while enhancing the hemostasis and healing capabilities is challenging to meet clinical needs.Herein,we designed the glucose-and catechol-functionalized derivatives from commercialε-polylysine(EPL)and prepared the hydrogels by simple amidation and catechol-crosslinking reactions,which have larger swelling ratios of 220%–240%,suitable microporous size of about 6–8µm,and tissue adhesion strength of about 20–40 kPa.The hemolysis,cytotoxicity,and cellular double-staining assays indicate that those hydrogels had good biocompatibility and the H-3 hydrogel with higher glucose content gave a lower hemolysis ratio of 0.73%±0.14%.The blood-clotting index,blood cell attachment and adhesion studies showed those hydrogels had fast blood-coagulation,resulting in excellent hemostasis performance with a short hemostatic time of 38–46 s and less blood loss of 19%–34%in a liver hemorrhage model.A full-thickness rat-skin defect model further demonstrates that the H-3 hydrogel achieved fast wound healing with a wound closure of 70.0%±2.7%on postoperative day 7 and nearly full closure on day 14.Remarkably,the hydroproline level that denotes the collagen production reached a higher one of 7.24±0.55µg/mg comparable to that in normal skins on day 14,evidencing the wound healing was close to completion in the H-3 treatment.Consequently,this work provides a simple method to construct a glycosylated and catechol-functionalized hydrogel platform from commercial EPL,holding translational potentials in wound hemostats and dressings.
基金financially supported by the National Natural Science Foundation of China(Nos.51222307,51303173,51390480,21474104 and 51403205)the Ministry of Science and Technology of China(International cooperation and communication program 2011DFR51090)Jilin Province Science and Technology Development Program(Nos.20120306,20130521011JH)
文摘Polyethylenimine-poly(L-lysine) (PEI-PLL) copolymer was synthesized via ring-opening polymerization of L-lysine N-carboxyanhydride (Lys(Z)-NCA) initiated by PEI. The complexation of PEI-PLL with siRNA was studied by particle size and zeta potential measurements. The flow cytometric analysis and confocal imaging showed its excellent intracellular trafficking ability. PEI-PLL displayed higher gene silencing efficiency and lower cytotoxicity than commercial PEI-25k in vitro. In the antitumor study, PEI-PLL was further combined with siVEGF and showed obviously tumor inhibition effect for the treatment of CT26 tumor model. Therefore, PEI-PLL is a promising siRNA carrier candidate for further antitumor treatment in vivo.
基金National Natural Science Foundation of China(Grant No.51773018,51973018)Key Research and Development Projects of People’s Liberation Army(BWS17J036).
文摘Cell transplantation is an effective strategy to improve the repair effect of nerve guide conduits(NGCs).However,problems such as low loading efficiency and cell anoikis undermine the outcomes.Microcarriers are efficient 3D cell culture scaffolds,which can also prevent cell anoikis by providing substrate for adhesion during transplantation.Here,we demonstrate for the first time microcarrier-based cell transplantation in peripheral nerve repair.We first prepared macroporous chitosan microcarriers(CSMCs)by the emulsion-phase separation method,and then decorated the CSMCs with polylysine(pl-CSMCs)to improve cell affinity.We then loaded the pl-CSMCs with adipose-derived stem cells(ADSCs)and injected them into electrospun polycaprolactone/chitosan NGCs to repair rat sciatic nerve defects.The ADSCs-laden pl-CSMCs effectively improved nerve regeneration as demonstrated by evaluation of histology,motor function recovery,electrophysiology,and gastrocnemius recovery.With efficient cell transplantation,convenient operation,and the multiple merits of ADSCs,the ADSCs-laden pl-CSMCs hold good potential in peripheral nerve repair.
基金financially supported by the National Basic Research Program(No.2014CB931900)the National Natural Science Foundation of China(No.21090352)
文摘Chirality is a key factor in the biological activity of many biomolecules. Poly(L-lysine)(PLL), a polypeptide synthesized from L-lysine, is one of the mostly used cationic polymers for gene delivery. The effect of chirality of polylysine(PL) on its gene delivery remains unknown. Herein, we prepared three polylysines(PLs) with the similar molecular weight but different backbone chiralities including poly(L-lysine)(PLL), poly(D-lysine)(PDL) and poly(DL-lysine)(PDLL). The side chains of each PL were modified with propylene oxide(PO) of different chiralities including(R)PO,(S)PO and(R,S)PO. These PL-POs with distinct chirality in main and side chains could condense p DNA into polyplexes. The polyplexes had approximately the same size, zeta potential and binding ability, but showed distinct gene transfection efficiency. We found that the PLs of L-configuration in the main chain had higher transfection efficiency than that of D or DL configuration due to their faster cellular uptake, while the side chain chirality had no effect on transfection efficiency.
基金supported by the National Natural Science Foundation of China (No. 21474061)the Innovation Program ofShanghai Municipal Education Commission (No. 201701070002E0061)the Innovation Fund (No. IFPM2016B004) of Shanghaijiao Tong University & Affiliated Sixth People’s Hospital South Campus are appreciated
文摘The ring-opening polymerization (ROP) of N-(tetrafluoroboran ammonium)-L-lysine-N-carboxyanhydride (NH3BF4-Lys NCA) was initiated by triethylamine to prepare hyperbranched polylysine (HPlys) fluoroborate with narrow polydispersity at a low temperature. Both mass spectroscopy analysis and DFT computation evidenced that the resultant cyclic dimer mainly initiated ROP as a secondary species according to normal amine mechanism. The hyperbranched polylysine in aqueous solution existed in a unimolecular state at low concentrations, but transformed into spherical micellar aggregates at a high concentration of 5 mg/mL, as characterized by dynamic laser scattering and transmission electron microscopy. By utilizing multivalent coordination interactions between hyperbranched polylysine and gold, the plasmonic gold nanoparticles (HPlys@Au NPs) were successfully prepared in aqueous solution, which elevated the solution by 23.1℃ upon 5 min of NIR laser irradiation (808 nm, 2 W/cm2).
文摘DTPA was covalently conjugated to the copolymer of L-lysine and L-tyrosine,then transchelated with Gd-EDTA,the resultant polymer chelates were further reacted with 6-O-bromoacetyl-D-galactose or methyl lactobionyloxyacetate to give PLT(Gd-DTPA)with galactose moiety as liver-targeting group.These macromolecular MRI contrast agents were characterized by means of FT-IR,ICP-AES,elementary analyses and UV-Vis spectrophotometry.Their in vitro relaxivity and liver targeting property in mice were also investigated.
文摘Oligo-(lysine) n (n = 1-4) containing different numbers of lysine residues was used to induce the condensation of silicic acid to form silica particles in neutral silicate solution. It was found that the condensation rate and the formation of silica particles are dependent on the number of lysine residues in an oligo-lysine. Oligo-lysine with more lysine residues can link more silicic acid together to form a matrix that promotes the effective aggregation of the condensed silica pieces to form large silica particles.
文摘It was found that microperoxidase-11 (MP-if) can undergo photoreduction at the bareroughened silver electrode. No photoreduction happens at the roughened silver electrodemodified with mercaptoundecanoic carboxylic acid/poly-lysine. The photoreduction mechanismis discussed.
基金the National Natural Science Foundation of China(Nos.51773201 and 51973212)the Bureau of Science and Technology of Changchun(No.19SS005)+1 种基金the Department of Science and Technology of Jilin Province(No.20200301017RQ)the Joint Program of CAS-Jilin Province(No.2019SYHZ0002).
文摘Medical devices-related infections pose a great threat to patients and cause an increased morbidity and mortality. Herein, we prepare an antibacterial composite(TPU-x) through blending medical grade thermoplastic polyurethane(TPU) and the complex(PL-DOSS) of ε-polylysine(ε-PL) and docusate sodium(DOSS). >99% reduction of colony forming unit(CFU) can be obtained in TPU-x composite films even at relatively low content of PL-DOSS, e.g. 0.13% for Methicillin resistant S. aureus(MRSA) and 0.5% for E. coli. The excellent antibacterial activity is mainly attributed to the formation of PL-DOSS nanoparticles that are uniformly dispersed in the TPU matrix with a size of ~100 nm. TPU-x composite films exhibit long-term stability in saline and good biocompatibility, and retain mechanical properties of TPU.