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

ABSTRACT (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.

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    • "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]. "
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    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
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    • "The study on drug delivery by nanoparticles is highly perspective of personalized medicine in the future [53]. Over the past decade, several delivery vehicles have been designed based on different nanomaterials, such as polymers [54], dendrimers [55], liposomes [56], nanotubes [57], and nanorods [58]. Therapeutic agents can also be coated onto the surface of gold nanoparticles. "
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    ABSTRACT: Nanoscale gold particles (AuNPs) have wide perspectives for biomedical applications because of their unique biological properties, as antioxidative activity and potentials for drug delivery.Aims and objectives: The aim was to test effects of AuNPs using suggested heart failure rat model to compare with proved medication Simdax, to test gold nanoparticle for drug delivery, and to test sonoporation effect to increase nanoparticles delivery into myocardial cells. We performed biosafety and biocompatibility tests for AuNPs and conjugate with Simdax. For in vivo tests, we included Wistar rats weighing 180--200 g (n = 54), received doxorubicin in cumulative dose of 12.0 mg/kg to model advance heart failure, registered by ultrasonography. We formed six groups: the first three groups of animals received, respectively, 0.06 ml Simdax, AuNPs, and conjugate (AuNPs-Simdax), intrapleurally, and the second three received them intravenously. The seventh group was control (saline). We performed dynamic assessment of heart failure regression in vivo measuring hydrothorax. Sonoporation of gold nanoparticles to cardiomyocytes was tested. We designed and constructed colloidal, spherical gold nanoparticles, AuNPs-Simdax conjugate, both founded biosafety (in cytotoxicity, genotoxicity, and immunoreactivity). In all animals of the six groups after the third day post-medication injection, no ascites and liver enlargement were registered (P < 0.001 vs controls). Conjugate injection showed significantly higher hydrothorax reduction than Simdax injection only (P < 0.01); gold nanoparticle injection showed significantly higher results than Simdax injection (P < 0.05). AuNPs and conjugate showed no significant difference for rat recovery. Difference in rat life continuity was significant between Simdax vs AuNPs (P < 0.05) and Simdax vs conjugate (P < 0.05). Sonoporation enhances AuNP transfer into the cell and mitochondria that were highly localized, superior to controls (P < 0.01 for both). Gold nanoparticles of 30 nm and its AuNPs-Simdax conjugate gave positive results in biosafety and biocompatibility in vitro and in vivo. AuNPs-Simdax and AuNPs have similar significant cardioprotective effects in rats with doxorubicin-induced heart failure, higher than that of Simdax. Intrapleural (local) delivery is preferred over intravenous (systemic) delivery according to all tested parameters. Sonoporation is able to enhance gold nanoparticle delivery to myocardial cells in vivo.
    07/2013; 4(1):20. DOI:10.1186/1878-5085-4-20
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    • "At physiological pH, positively charged terminal ammonium groups in PAMAM dendrimer can bind to negatively charged DNA phosphates to form a PAMAM/DNA complex (Hui et al., 2008). Studies using PEI and PAMAM dendrimer have indicated that these polymers have intrinsic nuclear targeting and localization activities (Lim et al., 1999; Wang et al., 2001; Xu et al., 2007; Patil et al., 2009). Cationic polymers may interact with negatively charged chromosomal DNA and adversely affect cell growth and nucleus function. "
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    ABSTRACT: A safe alternative to the viral system used in gene therapy is a nonviral gene delivery system. Although polyethylenimine (PEI) and polyamidoamine (PAMAM) dendrimer are among the most promising gene-carrier candidates for efficient nonviral gene delivery, safety concerns regarding their toxicity remain. The aim of this study was to scrutinize the underlying mechanism of the cytotoxicity and genotoxicity of PEI (25 kDa) and PAMAM (G4). To our knowledge, this is the first study to explore the genotoxic effect of polymeric gene carriers. To evaluate cell death by PEI and PAMAM, we performed propidium-iodide staining and lactate-dehydrogenase release assays. The genotoxicity of the polymers was measured by comet assay and cytokinesis-block micronucleus assay. PEI- and PAMAM-treated groups induced both necrotic and apoptotic cell death. In the comet assay and micronuclei formation, significant increases in DNA damage were observed in both treatments. We conclude that PEI and PAMAM dendrimer can induce not only a relatively weak apoptotic and a strong necrotic effect, but also a moderate genotoxic effect.
    Drug and Chemical Toxicology 10/2010; 33(4):357-66. DOI:10.3109/01480540903493507 · 1.23 Impact Factor
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