Polymer-iron oxide composite nanoparticles for EPR-independent drug delivery.
Nanoparticle (NP)-based approaches to cancer drug delivery are challenged by the heterogeneity of the enhanced permeability and retention (EPR) effect in tumors and the premature attrition of payload from drug carriers during circulation. Here we show that such challenges can be overcome by a magnetophoretic approach to accelerate NP delivery to tumors. Payload-bearing poly(lactic-co-glycolic acid) NPs were converted into polymer-iron-oxide nanocomposites (PINCs) by attaching colloidal Fe3O4 onto the surface, via a simple surface modification method using dopamine polymerization. PINCs formed stable dispersions in serum-supplemented medium and responded quickly to magnetic field gradients above 1 kG/cm. Under the field gradients, PINCs were rapidly transported across physical barriers and into cells and captured under flow conditions similar to those encountered in postcapillary venules, increasing the local concentration by nearly three orders of magnitude. In vivo magnetophoretic delivery enabled PINCs to accumulate in poorly vascularized subcutaneous SKOV3 xenografts that did not support the EPR effect. In vivo magnetic resonance imaging, ex vivo fluorescence imaging, and tissue histology all confirmed that the uptake of PINCs was higher in tumors exposed to magnetic field gradients, relative to negative controls.
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA; Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Jinho
J
Park
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
Naveen Reddy
NR
Kadasala
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA; Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Sara A
SA
Abouelmagd
Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Mark A
MA
Castanares
Lilly Research Laboratories, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN 46285, USA.
David S
DS
Collins
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA. Electronic address: alexwei@purdue.edu.
Alexander
A
Wei
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, IN 47907, USA; Weldon School of Biomedical Engineering, Purdue University, 206 South Martin Jischke Drive, West Lafayette, IN 47907, USA. Electronic address: yyeo@purdue.edu.
Yoon
Y
Yeo
D000818:Animals; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D052203:Ferrosoferric Oxide / Q000737:chemistry* / Q000493:pharmacokinetics; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000493:pharmacokinetics; D019344:Lactic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D008279:Magnetic Resonance Imaging; D008280:Magnetics / Q000379:methods; D051379:Mice; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy; D061848:Optical Imaging; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry* / Q000493:pharmacokinetics
D004337:Drug Carriers; D007211:Indoles; D011108:Polymers; C568283:polydopamine; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D052203:Ferrosoferric Oxide
In vivo delivery; Magnetic drug delivery; Polydopamine; Polymeric nanoparticles; Polymer–iron oxide nanocomposite