title: Design of Multifunctional Liposomal Nanocarriers for Folate Receptor-Specific Intracellular Drug Delivery.
abstract: As a novel carrier for folate receptor (FR)-targeted intracellular delivery, we designed two types of targetable liposomal systems using Pep-1 peptide (Pep1) and folic acid as a cell-penetrating peptide (CPP) and target molecule, respectively. Folate-linked Pep1 (Fol-Pep1) was synthesized by solid phase peptide synthesis (SPPS) and verified using (1)H NMR and far-ultraviolet (UV) circular dichroism (CD). The chimeric ligand (Fol-Pep1)-modified liposome (cF-P-L) was prepared by coupling Fol-Pep1 to maleimide-derivatized liposomes at various ratios. The dual ligand (folate and Pep1)-modified liposome (dF/P-L) was prepared by separately attaching both ligands to the liposomal surface via a short (PEG2000) or long (PEG3400) linker. The physical and conformational characteristics including vesicle size, zeta potential, and the number of conjugated ligands were determined. Intracellular uptake specificities of various fluorescent probe-containing cF-P-L and dF/P-L systems were assessed using FR-positive HeLa and FR-negative HaCaT cells. Cellular uptake behavior was visualized by confocal laser scanning microscopy (CLSM). Internalization was time-dependent. Fol-Pep1 and Pep-1 cytotoxicities were negligible up to 25 μM in FR-positive and FR-negative cells. Empty cF-P-L and dF/P-L were nontoxic at the concentration used. The optimized dF3/P2(450/90) system carrying 450 PEG3400-linked folate and 90 PEG2000-linked Pep1 molecules could be a good candidate for FR-specific intracellular drug delivery.
authors.affiliation: College of Pharmacy, Chung-Ang University , 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Min Hyung
authors.initials: MH
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chung-Ang University , 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Yoo
authors.affiliation: College of Pharmacy, Chung-Ang University , 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Yie Hyuk
authors.initials: YH
authors.lastname: Kwon
authors.affiliation: College of Pharmacy, Chung-Ang University , 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Ho Yub
authors.initials: HY
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, Chung-Ang University , 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Sang Gon
authors.initials: SG
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Chung-Ang University , 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Sung Rae
authors.initials: SR
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Chung-Ang University , 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Dong Woo
authors.initials: DW
authors.lastname: Yeom
authors.affiliation: College of Pharmacy, Dankook University , Cheonan-Si, Chungnam 330-714, Korea.
authors.forename: Myung Joo
authors.initials: MJ
authors.lastname: Kang
authors.affiliation: College of Pharmacy, Chung-Ang University , 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, Korea.
authors.forename: Young Wook
authors.initials: YW
authors.lastname: Choi
mesh_terms: D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D003543:Cysteamine / Q000031:analogs & derivatives / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005492:Folic Acid / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D008081:Liposomes / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D008024:Ligands; D008081:Liposomes; C503924:Pep-1 peptide; D010455:Peptides; D003543:Cysteamine; D005492:Folic Acid
keywords: Pep-1; cell penetrating peptide; drug targeting; dual-ligand; folic acid; intracellular delivery; liposome