Targeted Charge-Reversal Nanoparticles for Nuclear Drug Delivery

Department of Animal Science, University of Wyoming, Ларами, Wyoming, United States
Angewandte Chemie International Edition (Impact Factor: 11.26). 06/2007; 46(26):4999-5002. DOI: 10.1002/anie.200605254
Source: PubMed


(Figure Presented) Reversing the charges: Targeted charge-reversal nanoparticles (TCRNs) comprised of poly(ε-caprolactone)-block- polyethyleneimine (PCL-PEI), whose amine groups are converted into amides, are negatively charged at neutral pH but become positively charged at pH < 6 (see picture). TCRNs effectively enter cells, regenerate the PEI layer in lysosomes, and localize in the nucleus for nuclear drug delivery.

1 Follower
21 Reads
  • Source
    • "Amide linkage conjugated with a carbon–carbon double bond in position has been confirmed as an acid-cleavable bond due to intramolecular self-catalysis of carboxyl, which was commonly used in charge-reversal gene delivery systems [54] [55] [56]. Neuropilin- 1 (Nrp-1) is a transmembrane receptor glycoprotein which plays a predominant role in angiogenesis and vascular permeability. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Self-assembled prodrug nanoparticles have demonstrated great promise in cancer chemotherapy. In the present study, we developed a new kind of prodrug nanoparticles for targeted drug delivery. PEGylated doxorubicin conjugate with an acid-cleavable cis-aconityl spacer was prepared. Then it was functionalized with a tumor-penetrating peptide, Cys-Arg-Gly-Asp-Lys (CRGDK), providing the prodrug nanoparticles with the specific binding ability to neurophilin-1 receptor. In acid mediums, doxorubicin could be released from the prodrug nanoparticles with an accumulative release around 60% through the acid-triggered hydrolysis of cis-aconityl bond and nanoparticle disassembly. Whereas, drug release was slow under a neutral pH and the accumulative drug release was less than 16%. In the cell culture tests, our prodrug nanoparticles showed enhanced endocytosis and cytotoxicity in cancer cells including HepG2, MCF-7 and MDA-MB-231 cells, but lower cytotoxicity in human cardiomyocyte H2C9. In the animal experiments, the prodrug nanoparticles were intravenously injected into Balb/c nude mice bearing MDA-MB-231 tumors. Enhanced drug penetration and accumulation in tumors, accompanying with a rapid early tumor-binding behavior, was observed after intravenous injection of the peptide modified prodrug nanoparticles. These data suggests that the acid-sensitive and tumor-targeting PEGylated doxorubicin prodrug nanoparticle may be an efficient drug delivery system for cancer chemotherapy.
    Colloids and surfaces B: Biointerfaces 10/2015; 136:365-374. DOI:10.1016/j.colsurfb.2015.09.030 · 4.15 Impact Factor
  • Source
    • "However, HIV drugs, siRNA, and other proteins elicit their therapeutic outcomes efficiently when present in the cytoplasmic region [4] [10] [14]. Nuclear delivery often demands that the carrier nanoparticles must be tagged with cationic polymers [15] [16], TAT peptides [17] [18], or nuclear localization signals [19] [20] [21] [22] in addition to their drug load. In cytoplasmic delivery, for which endosomal escape is critical, the nanoparticles must be modified with cationic polymers/lipids [23] [24] [25], cell penetrating peptides (CPPs) [26] [27], pH-responsive carriers [28] or endosome disrupting agents [29] [30]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Targeted drug delivery to specific subcellular compartments of brain cells is challenging despite their importance in the treatment of several brain-related diseases. Herein, we report on shape-directed intracellular compartmentalization of nanoparticles in brain cells and their ability to deliver therapeutic molecules to specific organelles. Iron oxide (Fe3O4) nanoparticles with different morphologies (spheres, spindles, biconcaves, and nanotubes) were synthesized and coated with a fluorescent carbon layer derived from glucose (Fe3O4@C). In vivo studies showed that the Fe3O4@C nanoparticles with biconcave geometry localized predominantly in the nuclei of the brain cells, whereas those with nanotube geometry were contained mostly in the cytoplasm. Remarkably, a small-molecule activator of histone acetyltransferases delivered into the nuclei of the brain cells using nanoparticles with biconcave geometry showed enhancement in enzymatic activity by a factor of three and resulted in specific gene expression (transcription) compared with that of the molecule delivered to the cytoplasm using nanotube geometry. Copyright © 2015. Published by Elsevier B.V.
    Journal of Controlled Release 08/2015; 217. DOI:10.1016/j.jconrel.2015.08.043 · 7.71 Impact Factor
  • Source
    • "The ability of tuning the physicochemical properties of different classes of metallic and/or semiconductor nanoparticles by controlling their size in the nanoscale put them in the limelight of the modern biomedical research. Over the past years, several classes of nanoparticles: quantum dots, polymer nanoparticles [1], dendrimers [2], liposomes [3], nanotubes [4], and nanorods [5], have been synthesized and characterized . Owing to their unique properties (enhancement of Raman signal, size-tunable surface plasmon resonance, ease of preparation and of surface functionalization), gold nanoparticles (AuNPs) have become one of the most interesting candidates for modern biomedical applications such as biosensing, targeted drug delivery and photothermal therapy [6] [7]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The present work reports a rapid, simple and efficient one-step synthesis and detailed characterisation of stable aqueous colloids of gold nanoparticles (AuNPs) coated with unmodified poly(ethylene)glycol (PEG) molecules of different molecular weights and surface charges. By mixing and heating aqueous solutions of PEG with variable molecular chain and gold(III) chloride hydrate (HAuCl4) in the presence of NaOH, we have successfully produced uniform colloidal 5 nm PEG coated AuNPs of spherical shape with tunable surface charge and an average diameter of 30nm within a few minutes. It has been found out that PEGylated AuNPs provide optical enhancement of the characteristic vibrational bands of PEG molecules attached to the gold surface when they are excited with both visible (532 nm) and NIR (785 nm) laser lines. The surface enhanced Raman scattering (SERS) signal does not depend on the length of the PEGmolecular chain enveloping theAuNPs, and the stability of the colloid is not affected by the addition of concentrated salt solution (0.1M NaCl), thus suggesting their potential use for in vitro and in vivo applications. Moreover, by gradually changing the chain length of the biopolymer, we were able to control nanoparticles’ surface charge from −28 to −2mV, without any modification of the Raman enhancement properties and of the colloidal stability.
    Journal of Nanomaterials 09/2013; 2013. DOI:10.1155/2013/146031 · 1.64 Impact Factor
Show more