title: Beyond the imaging: limitations of cellular uptake study in the evaluation of nanoparticles.
abstract: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) conjugated to a cell-penetrating peptide, TAT, was used to increase intracellular delivery of paclitaxel (PTX) to multi-drug resistant (MDR) cells. Efficient cellular uptake of the TAT-conjugated PLGA NPs was observed; however, it did not translate to increased killing of MDR cells. An investigation of drug release kinetics in phosphate-buffered saline containing Tween 80 led us to suspect that a significant fraction of the loaded PTX was released before efficient cellular uptake could occur. These results indicate that the increased cellular uptake of NPs does not always mean an enhanced drug effect and that it is critical to control both the location of NPs and the drug release from NPs together. Based on this study, we propose that two prevalent practices in NP research be reconsidered: first, the utility of a new NP system should be tested beyond the imaging level. Second, NP release kinetics should be monitored in a medium that can reflect the complexity of biological environment rather than a simple buffered saline.
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, IN 47907, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Gullotti
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry; D003952:Diagnostic Imaging; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D018432:Drug Resistance, Multiple; D015696:Gene Products, tat / Q000737:chemistry; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D015696:Gene Products, tat; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D017239:Paclitaxel