Poly（caprolactone-b-2-vinylpyridine） （PCL-P2VP） coated with folate-conjugated M13 （FA-M13） provides a nanosized delivery system which is capable of encapsulating hydrophobic antitumor drugs such as doxorubicin ...Poly（caprolactone-b-2-vinylpyridine） （PCL-P2VP） coated with folate-conjugated M13 （FA-M13） provides a nanosized delivery system which is capable of encapsulating hydrophobic antitumor drugs such as doxorubicin （DOX）. The DOXqoaded FA-M13-PCL-P2VP assemblies had an average diameter of approximately 200 nm and their structure was characterized using transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The particles were stable at physiological pH but could be degraded at a lower pH. The release of DOX from the nanoassemblies under acidic conditions was shown to be significantly faster than that observed at physiological pH. In addition, the DOX-loaded FA-M13-PCL-P2VP particles showed a distinctly greater cellular uptake and cytotoxicity against folate-receptor-positive cancer cells than folate-receptor-negative cells, indicating that the receptor facilitates folate uptake via receptor-mediated endocytosis. Furthermore, the DOX-loaded particles also had a significantly higher tumor uptake and selectivity compared to free DOX. This study therefore offers a new way to fabricate nanosized drug delivery vehicles.展开更多
Biocompatible and biodegradable ε-poly-L- lysine （EPL）/poly （ε-caprolactone） （PCL） copolymer was designed and synthesized. The amphiphilic EPL-PCL copolymer could easily self-assembled into monodispersed nanop...Biocompatible and biodegradable ε-poly-L- lysine （EPL）/poly （ε-caprolactone） （PCL） copolymer was designed and synthesized. The amphiphilic EPL-PCL copolymer could easily self-assembled into monodispersed nanoparticles （NPs）, which showed a broad-spectrum antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis. Interestingly, the antibacterial efficacy of the novel NPs is more potent than the cationic peptide EPL. To explore the underlying mechanism of the biodegradable cationic NPs, various possible antibacterial pathways have been validated. The NPs have been found that they can disrupt bacterial walls/ membranes and induce the increasing in reactive oxygen species and alkaline phosphatase levels. More importantly, the self-assembled NPs induced the changes in bacterial osmotic pressure, resulting in cell invagination to form holes and cause the leakage of cytoplasm. Taken together, our results suggest that the EPL-PCL NPs can be further developed to be a promising antimicrobial agent to treat infectious diseases as surfactants and emulsifiers to enhance drug encapsulation efficiency and antimicrobial activity.展开更多
基金We are grateful for financial support from the US National Science Foundation （NSF） （CAREER program and No. DMR-0706431）, US Department of Defense （DoD） （No. W911NF-09-1-0236）, the Alfred P. Sloan Scholarship, the Camille Dreyfus Teacher-Scholar Award, DoD-Army Research Office （ARO）, and the W. M. Keck Foundation. We are also indebted to Dr. Udai Singh for assistance with flow cytometry and Laying Wu for TEM and SEM analyses.
文摘Poly（caprolactone-b-2-vinylpyridine） （PCL-P2VP） coated with folate-conjugated M13 （FA-M13） provides a nanosized delivery system which is capable of encapsulating hydrophobic antitumor drugs such as doxorubicin （DOX）. The DOXqoaded FA-M13-PCL-P2VP assemblies had an average diameter of approximately 200 nm and their structure was characterized using transmission electron microscopy, scanning electron microscopy, and dynamic light scattering. The particles were stable at physiological pH but could be degraded at a lower pH. The release of DOX from the nanoassemblies under acidic conditions was shown to be significantly faster than that observed at physiological pH. In addition, the DOX-loaded FA-M13-PCL-P2VP particles showed a distinctly greater cellular uptake and cytotoxicity against folate-receptor-positive cancer cells than folate-receptor-negative cells, indicating that the receptor facilitates folate uptake via receptor-mediated endocytosis. Furthermore, the DOX-loaded particles also had a significantly higher tumor uptake and selectivity compared to free DOX. This study therefore offers a new way to fabricate nanosized drug delivery vehicles.
基金supported by the National Basic Research Program of China(2012CB934000,2011CB933400)the National Natural Science Foundation of China(31325010,21277037)
文摘Biocompatible and biodegradable ε-poly-L- lysine （EPL）/poly （ε-caprolactone） （PCL） copolymer was designed and synthesized. The amphiphilic EPL-PCL copolymer could easily self-assembled into monodispersed nanoparticles （NPs）, which showed a broad-spectrum antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis. Interestingly, the antibacterial efficacy of the novel NPs is more potent than the cationic peptide EPL. To explore the underlying mechanism of the biodegradable cationic NPs, various possible antibacterial pathways have been validated. The NPs have been found that they can disrupt bacterial walls/ membranes and induce the increasing in reactive oxygen species and alkaline phosphatase levels. More importantly, the self-assembled NPs induced the changes in bacterial osmotic pressure, resulting in cell invagination to form holes and cause the leakage of cytoplasm. Taken together, our results suggest that the EPL-PCL NPs can be further developed to be a promising antimicrobial agent to treat infectious diseases as surfactants and emulsifiers to enhance drug encapsulation efficiency and antimicrobial activity.
