Polyol-Based Synthesis of Praseodymium Oxide Nanoparticles
225. Gu F, Zhang L, Teply BA, Mann N, Wang A, Radovic-Moreno AF. . Precise engineering of targeted nanoparticles by using self-assembled biointegrated block copolymers. 2008;105:2586-91
Polyol Synthesis and Properties of AFe2O4 Nanoparticles …
It has become increasingly clear that the tumor-targeting properties of the nanoparticles optimized are not predictive of the performance. Farokhzad and Langer identified maximally targeted and maximally stealth surface engineering conditions for and performance using PSMA targeted aptamer-conjugated Dtxl-loaded self-assembled nanoparticles . Nanoparticles were prepared with different compositions of the self-assembled diblock copolymers and aptamers, and the optimal aptamer density on the nanoparticle surface was initially determined . Increasing the ligand density to 5% significantly increased the nanoparticle uptake by the target cells (LNCaP), whereas further increase in aptamer density modestly increased the nanoparticle uptake. These results indicated that the optimum ligand density for PSMA-specific endocytosis was 10-80 nmol aptamer per μmol nanoparticle. LNCaP xenograft mouse models injected with the targeted nanoparticles showed that increasing the aptamer density from 0% to 5% significantly increased nanoparticle retention in tumors, but the retention decreased for aptamer densities beyond 10%. The authors suggested that higher aptamer densities may have reduced the nanoparticle stealth properties, resulting in rapid clearance by the liver. Gabizon . optimized the ligand density in the Her2-targeted PEGylated liposomal Dox system (HT-PLD) for ligand ratios of 7.5, 15, or 30 per liposome . The best safety margin and performance resulted from a ligand density of 15 ligands per liposome in the HT-PLD formulation. A 30 ligand ratio accelerated plasma clearance in the tumor-bearing mice, and the 7.5 ligand ratio reduced cytotoxicity after passage.
Pyridyl disulfide linkers include cleavable disulfide bonds, which facilitates a quantitative evaluation of the reaction efficiency. Jon . calculated the concentration of surface-bound peptide molecules on the nanoparticles by quantifying the released pyridine-2-thione . In an effort to develop integrin-targeted iron oxide nanoparticles as theranostic agents, amine-modified iron oxide nanoparticles were synthesized, and SPDP was added to convert the primary amine groups on the nanoparticles to sulfhydryl-reactive pyridyldisulfide groups. Conjugation between the thiol group-containing cyclic RGD peptides and the SPDP-activated nanoparticles produced pyridine-2-thione, which was immediately collected by spin filtering (at 100 K). The immobilized cRGD molecules were quantified based on the ultraviolet (UV) absorbance at 343 nm of the collected pyridine-2-thione filtrate, indicating that the average number of conjugated cRGD peptides on each nanoparticle was 0.39 wt%. This linker is useful for enhancing the intracellular gene silencing properties of siRNA. Bhatia . studied the gene-silencing efficacy of siRNA-conjugated QDs using cleavable (sulfo-LC-SPDP) or noncleavable (sulfo-SMCC) cross-linkers . They immobilized thiol-modified siRNA specific for EGFP to amine-functionalized QDs via sulfo-LC-SPDP or sulfo-SMCC linkers and quantified the EGFP fluorescence intensity. The siRNA attached QDs via the sulfo-LC-SPDP linker provided greater silencing efficiency than those attached via the sulfo-SMCC linker. The cleavable disulfide cross-linker released siRNA from the nanoparticles into the intracellular reducing environment, which affected the interactions between the siRNA and the RNA induced silencing complex (RISC), which is necessary for gene knockdown.
Polyol synthesis of nanoparticles – …
Li . designed folate receptor-targeted hollow gold nanospheres carrying siRNA recognizing NF-B, a transcription factor related to the expression of genes involved in tumor development [,]. In this case, the photothermal effects of gold nanospheres were utilized to regulate drug release and as a therapeutic tool. Core/shell-structured hollow gold nanospheres (HAuNS, 40 nm) were initially synthesized, consisting of a thin gold wall with a hollow interior, and the structures displayed strong surface plasmon resonance (SPR) tunability in the near-IR region [-]. Thiol-modified siRNA duplexes directed toward the NF-B p65 subunit were then introduced to the surface of HAuNS. Folates were coupled to the nanoparticles through a thioctic acid-terminated PEG linker to produce F-PEG-HAuNS-siRNA (Figure A and B). Irradiation with a pulsed near-IR laser (800 nm) altered the absorption spectra of the HAuNS-siRNA solutions significantly, indicating a loss in the structural integrity and triggering the dissociation of siRNA from HAuNS, when demonstrated by TEM and fluorescence microscopy images. This mode of action is termed 'photothermal transfection'. Intravenous injection of the nanospheres into HeLa xenografts resulted in the distinct downregulation of the NF-B p65 subunit only for the folate-conjugated nanosphere treatment combined with near-IR laser irradiation, suggesting that selective targeting and endolysosomal escape of the nanoparticles was activated by near-IR irradiation at the tumor site. tests, in which therapy was combined with administration of irinotecan, a chemotherapeutic agent that increases sensitivity to NF-B inhibition, yielded a substantially enhanced apoptotic response (Figure C). micro-positron emission tomography (PET))/computed tomography (CT) imaging also confirmed the folate-mediated tumor-targeted theranostic properties of the nanostructures (Figure D). Although significant uptake of the nanoparticles was observed in the liver, spleen, kidney, and lung, no significant downregulation of p65 in these organs was observed as a result of the tumor-selective near-IR irradiation.
Polyol-Mediated Synthesis of Zinc Oxide Nanorods and ..
Wei and Gao used a single chain anti-prostate stem cell antigen (PSCA) antibody (scAbPSCA) as a specific 'address tag' for prostate cancer targeted imaging and therapy . Prostate stem cell antigen is a prostate-specific glycosyl phosphatidylinositol-anchored glycoprotein that is marginally expressed in normal prostate and overexpressed in prostate cancer tissues . As shown in Figure A, the scAbPSCA was prepared by cleaving intact AbPSCA with mercaptoethylamine (MEA), followed by linking to maleimide-PEG-carboxyl (MAL-PEG-COOH) and covalent conjugation to multifunctional polymeric vesicles that had been formed by the entrapping of superparamagnetic iron oxide (SPIO) nanoparticles and docetaxel (Dtxl) by amine-terminated poly(lactic-co-glycolic) acid. The scAbPSCA-Dtxl/SPIO-NPs were 147 nm in size, as determined by dynamic light scattering (DLS), and the amounts of SPIOs and Dtxl in the polymer matrix were 23 wt% and 6.02 wt%, respectively. The high drug encapsulation efficiency was due to partitioning of Dtxl into the oleic acid and oleylamine shell of the SPIOs, which acted as a drug reservoir, thereby exhibiting a triphasic drug release pattern rather than the common two-phase kinetic release pattern, including burst effects of an initial release stage, as observed in vesicles without SPIOs. An cytotoxicity study demonstrated the antiproliferative effects of the multifunctional vesicles toward prostate cancer cells. As indicated in Figures B and C, PC3 cells incubated with scAbPSCA-Dtxl/SPIO-NPs produced distinct darkened regions in the T2-weighted MRI compared to the polymeric vesicles without scAbPSCA or Endorem® (a commercial contrast, Guerbet, France). This result demonstrated that the scAbPSCA-Dtxl/SPIO-NPs could be used as MRI contrast agents for prostate-targeted imaging and real-time monitoring of therapeutic effects.