Paclitaxel-loaded, folic-acid-targeted and TAT-peptide-conjugated polymeric liposomes: in vitro and in vivo evaluation.
OBJECTIVE
Folic acid and TAT peptide were conjugated on the octadecyl-quaternized, lysine-modified chitosan-cholesterol polymeric liposomes (FA-TATp-PLs) to investigate their potential feasibility for tumor-targeted drug delivery.


METHODS
FA-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) 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.


RESULTS
Our data showed that 80% paclitaxel released from FA-TATp-PLs in 2 weeks. Different from other various PLs, CLSM analyses showed that FA-TATp-PLs had a significantly high efficient intracellular uptake in both KB and A549 cells. These data revealed the targeting effects of folate decoration, the transmembrane ability of TAT peptide as well as a synergistic interaction between them. In addition, paclitaxel-loaded FA-TATp-PLs exhibited a more superior antitumor effect in vitro and in vivo as compared to that with Taxol.


CONCLUSIONS
FA-TATp-PLs possessing both targeting effect and transmembrane ability may serve as a promising carrier for the intracellular delivery of therapeutic agents.
Zhao
Peiqi
P
The Key Laboratory of Breast Cancer Prevention and Therapy Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China.
Wang
Hanjie
H
Yu
Man
M
Cao
Shuzhen
S
Zhang
Fei
F
Chang
Jin
J
Niu
Ruifang
R
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000031:analogs & derivatives*; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005260:Female; D058973:Folate Receptors, GPI-Anchored / Q000096:biosynthesis; D005492:Folic Acid / Q000737:chemistry*; D015696:Gene Products, tat / Q000737:chemistry*; D006801:Humans; D007624:KB Cells; D008081:Liposomes; D051379:Mice; D016513:Mice, SCID; D046529:Microscopy, Electron, Transmission; D017239:Paclitaxel / Q000008:administration & dosage* / Q000494:pharmacology; D012995:Solubility; D013499:Surface Properties; D023041:Xenograft Model Antitumor Assays
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D015696:Gene Products, tat; D008081:Liposomes; D048271:Chitosan; D005492:Folic Acid; D017239:Paclitaxel