title: A simple and general method for preparing antibody-PEG-PLGA sub-micron particles using electrospray technique: an in vitro study of targeted delivery of cisplatin to ovarian cancer cells.
abstract: Cisplatin-encapsulating maleimide-polyethylene glycol- Poly(d,l-lactic-co-glycolide) (cis-encapsulating mal-PEG-PLGA) particles were produced using the electrospray technique and bioconjugated with CD44 monoclonal antibody, targeting the counterpart receptor. The produced suspension of cis-encapsulating CD44-PEG-PLGA particles contains an antibody loading of 12.65-15.17 μg/mL and efficiently targets a CD44-overexpressed ovarian cancer cell line, such as CP70 and SKOV-3, within 6h of treatment, which was determined by Bradford assay, immunofluorescence analysis, and confocal laser scanning microscopic (CLSM) study. Most importantly, no tedious multi-step bioconjugation procedures are needed to synthesize mal-PEG-PLGA vehicles for antibody and drug loading, avoiding the undesirable hydrolysis of mal-PEG moiety and so successfully generating the cis-encapsulating mal-PEG-PLGA particles within one step. After conjugation of the CD44 antibody, the produced cis-encapsulating CD44-PEG-PLGA particles exhibited a better anti-proliferative ability against ovarian cancer cells compared to free form of cisplatin and PLGA particles without CD44 conjugation. Notably, the cis-encapsulating CD44-PEG-PLGA particles have approximately 10-14% greater the anti-proliferative ability against CP70 and SKOV-3 cells at a concentration of 1.25 μM, which falls within the concentrations used in chemotherapy. The proposed antibody-functionalization strategy represents an excellent platform for preparing particles with targeting ability in cancer therapy in vitro or in vivo.
authors.affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan, ROC; Adjunct appointment to the Department of Biomedical Engineering, National Defense Medical Center, Taipei 11490, Taiwan, ROC. Electronic address: mybai@mail.ntust.edu.tw.
authors.forename: Meng-Yi
authors.initials: MY
authors.lastname: Bai
authors.affiliation: Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan, ROC.
authors.forename: Sheng-Zhong
authors.initials: SZ
authors.lastname: Liu
mesh_terms: D000906:Antibodies / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D019344:Lactic Acid / Q000737:chemistry*; D008301:Maleimides / Q000737:chemistry; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000906:Antibodies; D018960:Hyaluronan Receptors; D008301:Maleimides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C043592:maleimide; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D016650:Fluorescein-5-isothiocyanate; D002945:Cisplatin
keywords: Biomaterials; Controlled release; Drug delivery; Electrospray; Nanotechnology