Multifunctional nanoparticles of paclitaxel and cyclodextrin- polypeptide conjugates with in vitro anticancer activity.

In this study, the cyclodextrin polypeptide (R8-CM beta CD) was successfully synthesized by the conjugation of a cell-penetrating peptide (R8) with carboxymethyl-beta-cyclodextrin (CM beta CD) via the carbon diamine reaction. Then, paclitaxel-loaded nanoparticles (PTX@R8-CM beta CD NPs) was prepared. Results of transmission electron microscopy (TEM) showed that PTX@R8-CM beta CD NPs were spherical with smooth surfaces and an average diameter about 144 nm. The amount of PTX released from NPs was less than 20% at pH7.4, but it increased significantly to 80% in the weakly acidic cytoplasm of tumors (pH5.0). Furthermore, PTX@R8-CM beta CD NPs promoted the cellular uptake of PTX. Further studies on the mechanism showed that cellular uptake of PTX@R8-CM beta CD NPs could rely on multiple pathways. In addition, the NPs had the ability to inhibit P-gp efflux pumps. Cytotoxicity tests showed that the NPs had no side effects. Taken together, PTX@R8-CM beta CD NPs is an effective anticancer drug delivery system, and the material (R8-CM beta CD) may be a promising anti-cancer drug carrier.