title: Uptake and intracellular fate of multifunctional nanoparticles: a comparison between lipoplexes and polyplexes via quantum dot mediated Förster resonance energy transfer.
abstract: Lipoplexes and polyplexes represent the two major nanocarrier systems for nucleic acid delivery. Previous studies examining their uptake and intracellular unpacking rely on organic fluorophores fraught with low signal intensity and photobleaching. In this work quantum dot mediated Förster resonance energy transfer (QD-FRET) was first used to study and compare the cellular uptake and the intracellular fate of oligodeoxynucelotide (ODN)-based lipoplexes and polyplexes. QD605-amine and Cy5-labeled ODN (Cy5-GTI2040) were chosen as the FRET pair. By adjusting the lipid/ODN ratio of lipoplexes and the nitrogen/phosphate (N/P) ratio of polyplexes, lipoplexes and polyplexes with comparable physical properties were produced. The biological activities of dual-labeled lipoplexes and polyplexes remained unaltered compared to their unlabeled counterparts as evidenced by their comparable antisense activities against protein R2 in KB cells. Flow cytometry and confocal microscopy revealed similar pattern of uptake for these two types of nanoparticles, although polyplexes had a higher dissociation rate than lipoplexes in KB cells. We demonstrate that QD-FRET is a sensitive tool to study the uptake and intracellular unpacking of lipoplexes and polyplexes, which may help optimize their formulations for various theranostics applications.
authors: Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, 174 West 18th Avenue, Columbus, Ohio 43210, United States.
authors: Yun
authors: Y
authors: Wu
authors: Yi-Ping
authors: YP
authors: Ho
authors: Yicheng
authors: Y
authors: Mao
authors: Xinmei
authors: X
authors: Wang
authors: Bo
authors: B
authors: Yu
authors: Kam W
authors: KW
authors: Leong
authors: L James
authors: LJ
authors: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D002470:Cell Survival / Q000187:drug effects; D055598:Chemical Phenomena; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D031541:Fluorescence Resonance Energy Transfer; D005456:Fluorescent Dyes / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007624:KB Cells; D008055:Lipids / Q000737:chemistry*; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000009:adverse effects / Q000737:chemistry* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000648:ultrastructure; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism*; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry*; D045663:Quantum Dots; D012333:RNA, Messenger / Q000378:metabolism; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013499:Surface Properties
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008055:Lipids; D009363:Neoplasm Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D011094:Polyethyleneimine; D012264:Ribonucleotide Reductases; C108427:ribonucleotide reductase R2 subunit