title: PEGylated J591 mAb loaded in PLGA-PEG-PLGA tri-block copolymer for targeted delivery: in vitro evaluation in human prostate cancer cells.
abstract: J591 monoclonal antibody (mAb) has high affinity for prostate specific membrane antigen (PSMA) on prostate cancer (PCA) cells. We coupled polyethylene glycol-J591 (PEGylated J591) to a salicyl hydroxamic acid (SHA)-derivatized polyethylenimine (PEI)/DNA-betagal vector to investigate the specificity and efficiency of targeting PSMA in PCA cells through encapsulation. Coupling was facilitated via the high affinity interaction between phenyl(di)boronic acid (PDBA) and SHA molecules yielding J591/PEG/PEI/DNA-betagal polyplex. After encapsulation with poly(d,l-lactic-co-glycolic acid)-b-polyethylene glycol-b-poly(d,l-lactic-co-glycolic acid) (PLGA-PEG-PLGA) tri-block copolymer, 8-10-fold increment of gene transfection levels were attained at the optimum concentration of 0.25% (w/v) using Pluronic F68 tri-block copolymer as a control. The enhanced transfection efficiency was attributed to increased internalization and uptake of the radiolabeled plasmid in the presence of PLGA-PEG-PLGA tri-block copolymer. The release of plasmid DNA (pDNA) from microparticles containing SHA-PEI-complexed pDNA showed little initial burst release followed by a 5% release over 48 h. The release accelerated thereafter and approximately 60% was released after 28 days. Deconvolution confocal microscopy showed polyplex/microparticle formulation localized in the cell nucleus as opposed to the polyplex without PLGA-PEG-PLGA indicating that an optimal concentration of PLGA-PEG-PLGA tri-block copolymer can be utilized to enhance endocytic process of J591-mediated targeting of PCA cells.
authors.affiliation: Laboratory of Experimental Therapeutics, Department of Genitourinary Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, 77030, USA. Stanley-moffatt@excite.com
authors.forename: Stanley
authors.initials: S
authors.lastname: Moffatt
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cristiano
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D010957:Plasmids; D011092:Polyethylene Glycols / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011471:Prostatic Neoplasms; D014162:Transfection / Q000379:methods
chemical_list: D000911:Antibodies, Monoclonal; C478680:J591 monoclonal antibody; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D004247:DNA