title: Multifunctional liquid crystal nanoparticles for intracellular fluorescent imaging and drug delivery.
abstract: A continuing goal of nanoparticle (NP)-mediated drug delivery (NMDD) is the simultaneous improvement of drug efficacy coupled with tracking of the intracellular fate of the nanoparticle delivery vehicle and its drug cargo. Here, we present a robust multifunctional liquid crystal NP (LCNP)-based delivery system that affords facile intracellular fate tracking coupled with the efficient delivery and modulation of the anticancer therapeutic doxorubicin (Dox), employed here as a model drug cargo. The LCNPs consist of (1) a liquid crystal cross-linking agent, (2) a homologue of the organic chromophore perylene, and (3) a polymerizable surfactant containing a carboxylate headgroup. The NP core provides an environment to both incorporate fluorescent dye for spectrally tuned particle tracking and encapsulation of amphiphilic and/or hydrophobic agents for intracellular delivery. The carboxylate head groups enable conjugation to biologicals to facilitate the cellular uptake of the particles. Upon functionalization of the NPs with transferrin, we show the ability to differentially label the recycling endocytic pathway in HEK 293T/17 cells in a time-resolved manner with minimal cytotoxicity and with superior dye photostability compared to traditional organic fluorophores. Further, when passively loaded with Dox, the NPs mediate the rapid uptake and subsequent sustained release of Dox from within endocytic vesicles. We demonstrate the ability of the LCNPs to simultaneously serve as both an efficient delivery vehicle for Dox as well as a modulator of the drug's cytotoxicity. Specifically, the delivery of Dox as a LCNP conjugate results in a ∼40-fold improvement in its IC50 compared to free Dox in solution. Cumulatively, our results demonstrate the utility of the LCNPs as an effective nanomaterial for simultaneous cellular imaging, tracking, and delivery of drug cargos.
authors: Center for Bio/Molecular Science and Engineering, Naval Research Laboratory , 4555 Overlook Avenue Southwest, Washington, D.C., 20375, United States.
authors: Christopher M
authors: CM
authors: Spillmann
authors: Jawad
authors: J
authors: Naciri
authors: W Russ
authors: WR
authors: Algar
authors: Igor L
authors: IL
authors: Medintz
authors: James B
authors: JB
authors: Delehanty
mesh_terms: D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D004705:Endocytosis; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D050866:Liquid Crystals / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D061848:Optical Imaging / Q000379:methods*; D014168:Transferrin / Q000737:chemistry / Q000378:metabolism
chemical_list: D004337:Drug Carriers; D014168:Transferrin; D004317:Doxorubicin