| ObjectivesThe design and construction of more effective drug delivery system are very important. Multifunctional targeted drug delivery systems, such as polymeric liposomes (PLs) and trans-activating transcriptional activator protein (TAT) conjugated PLs and folate conjugated PLs, were designed by using Octadecyl quaternized lysine modified chitosan (OQLCS) and its derivatives (FA-OQLCS,TATp-OQLCS). We evaluated the in vitro paclitaxel release, targeted delivery, in vitro and in vivo anti-tumor activity of paclitaxel loaded FA-TATp-PLs by a series of in vitro and in vivo experiments.MethodsFA-TATp-PLs encapsulating paclitaxel or calcein were synthesized and characterized. Cellular uptake of PLs, FA-PLs, TATp-PLs and FA-TATp-PLs was studied by confocal laser scanning microscopy (CLSM) and flow cytometry in folate receptor (FR)-positive KB nasopharyngeal epidermal carcinoma cells and FR-deficient A549 lung cancer cells. In vitro and in vivo antitumor activity of paclitaxel-loaded FA-TATp-PLs were also evaluated in KB and A549 cells as well as in a murine KB xenograft model.ResultsFA-TATp-PLs were prepared by the thin-film hydration method using FA-OQLCS,TATp-OQLCS and cholesterol. Our data showed that 80% paclitaxel released from FA-TATp-PLs in 2 weeks. Different from other various PLs, CLSM and flow cytometry analyses showed that FA-TATp-PLs had a more efficient intracellular uptake in both FR-positive KB and FR-negative A549 cells. These data demonstrated the targeting effects of folate decoration, the transmembrane ability of TAT peptide as well as a synergistic interaction between them. Compared to that with Taxol, paclitaxel-loaded FA-TATp-PLs exhibited a more superior antitumor activity.Conclusions FA-TATp-PLs possessing both targeting effect and transmembrane ability may serve as a promising carrier for the intracellular delivery of therapeutic agents and paclitaxel-loaded FA-TATp-PLs will be a promising nano-sized drug formulation for future cancer therapy. |
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