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
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.
