Characterization of Biomolecular Nanoconjugates by High-Throughput Delivery and Spectroscopic Difference

Delong, Robert K.; Azure, Risor,; Masaaki, Kanomata,; Laymon, Amanda; Jones, Brooke; Zimmerman, Scott; Williams, Joseph F.; Witkowski, C. M.; Mathew, Warner,; Ruff, Michael W.; Garrad, Richard C.; Fallon, John K.; Hickey, Anthony; Sedaghat‐Herati, Reza

doi:10.2217/nnm.12.70

Cited by 63 publications

(18 citation statements)

References 25 publications

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“…The particle size was found to be an important parameter regarding particle uptake. The small nanoparticle size may provide a large surface area and increase in mucin adsorption, which leads to a high mucoadhesive property for the nanoparticles [34]. The permeability of the particles through the intestinal mucosa decreases with increasing particle size reaching a cut-off at around 500 nm [35,36].…”

Section: Resultsmentioning

confidence: 99%

Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

Jiang

Liu

et al. 2013

Nanoscale Res Lett

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Oral chemotherapy is a key step towards ‘chemotherapy at home’, a dream of cancer patients, which will radically change the clinical practice of chemotherapy and greatly improve the quality of life of the patients. In this research, three types of nanoparticle formulation from commercial PCL and self-synthesized d-α-tocopheryl polyethylene glycol 1000 succinate (PLA-PCL-TPGS) random copolymer were prepared in this research for oral delivery of antitumor agents, including thiolated chitosan-modified PCL nanoparticles, unmodified PLA-PCL-TPGS nanoparticles, and thiolated chitosan-modified PLA-PCL-TPGS nanoparticles. Firstly, the PLA-PCL-TPGS random copolymer was synthesized and characterized. Thiolated chitosan greatly increases its mucoadhesiveness and permeation properties, thus increasing the chances of nanoparticle uptake by the gastrointestinal mucosa and improving drug absorption. The PLA-PCL-TPGS nanoparticles were found by FESEM that they are of spherical shape and around 200 nm in diameter. The surface charge of PLA-PCL-TPGS nanoparticles was reversed from anionic to cationic after thiolated chitosan modification. The thiolated chitosan-modified PLA-PCL-TPGS nanoparticles have significantly higher level of the cell uptake than that of thiolated chitosan-modified PLGA nanoparticles and unmodified PLA-PCL-TPGS nanoparticles. In vitro cell viability studies showed advantages of the thiolated chitosan-modified PLA-PCL-TPGS nanoparticles over Taxol® in terms of cytotoxicity against A549 cells. It seems that the mucoadhesive nanoparticles can increase paclitaxel transport by opening tight junctions and bypassing the efflux pump of P-glycoprotein. In conclusion, PLA-PCL-TPGS nanoparticles modified by thiolated chitosan could enhance the cellular uptake and cytotoxicity, which revealed a potential application for oral chemotherapy of lung cancer.

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Section: Resultsmentioning

confidence: 99%

Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

Jiang

Liu

et al. 2013

Nanoscale Res Lett

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“…27,40 The A375 pLuc cells constitutively express a nonfunctional, aberrantly spliced luciferase protein. Upon delivery of the 705 SSO, correct luciferase splicing is restored, and the cells produce a functional protein whose activity can be measured by assaying for luciferase activity.…”

Section: Resultsmentioning

confidence: 99%

mPEG-PAMAM-G4 Nucleic Acid Nanocomplexes: Enhanced Stability, RNase Protection, and Activity of Splice Switching Oligomer and Poly I:C RNA

et al. 2013

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Dendrimer chemistries have virtually exploded in recent years with increasing interest in this class of Polymers as gene delivery vehicles. An effective nucleic acid delivery vehicle must efficiently bind its cargo and form physically stable complexes. Most importantly, the nucleic acid must be protected in biological fluids and tissues, as RNA is extremely susceptible to nuclease degradation. Here, we characterized the association of nucleic acids with generation 4 PEGylated Poly(amidoamine)dendrimer (mPEG-PAMAM-G4). We investigated the formation, size, and stability over time of the nanoplexes at various N/P ratios by gel shift and dynamic light scatter spectroscopy (DLS). Further characterization of the mPEG-PAMAM-G4:nucleic acid association was provided by atomic force microscopy (AFM) and by circular dichroism (CD). Importantly, mPEG-PAMAM-G4 complexation protected RNA from treatment with RNase A, degradation in serum and various tissue homogenates. mPEG-PAMAM-G4 complexation also significantly enhanced the functional delivery of RNA in a novel engineered human melanoma cell line with splice-switching oligonucleotides (SSOs) targeting a recombinant luciferase transcript. mPEG-PAMAM-G4 triconjugates formed between gold nanoparticle (GNP) and particularly manganese oxide (MnO) nanorods, Poly IC, an anti-cancer RNA, showed enhanced cancer-killing activity by an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell viability assay.

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“…They are formed by one or several closed concentric bilayers made of phospholipids possessing hydrophobic tails and hydrophilic heads, which limit the inner aqueous phase. Liposomes have been successfully used for delivery of water-soluble substances placed in their hydrophilic core [113, 114]. …”

Section: Lipid-based Delivery Systemsmentioning

confidence: 99%

Non-Viral Delivery and Therapeutic Application of Small Interfering RNAs

Никитенко

Prassolov

2013

Acta Naturae

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RNA interference (RNAi) is a powerful method used for gene expression regulation. The increasing knowledge about the molecular mechanism of this phenomenon creates new avenues for the application of the RNAi technology in the treatment of various human diseases. However, delivery of RNA interference mediators, small interfering RNAs (siRNAs), to target cells is a major hurdle. Effective and safe pharmacological use of siRNAs requires carriers that can deliver siRNA to its target site and the development of methods for protection of these fragile molecules from in vivo degradation. This review summarizes various strategies for siRNA delivery, including chemical modification and non-viral approaches, such as the polymer-based, peptide-based, lipid-based techniques, and inorganic nanosystems. The advantages, disadvantages, and prospects for the therapeutic application of these methods are also examined in this paper.

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Characterization of Biomolecular Nanoconjugates by High-Throughput Delivery and Spectroscopic Difference

Cited by 63 publications

References 25 publications

Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

Thiolated chitosan-modified PLA-PCL-TPGS nanoparticles for oral chemotherapy of lung cancer

mPEG-PAMAM-G4 Nucleic Acid Nanocomplexes: Enhanced Stability, RNase Protection, and Activity of Splice Switching Oligomer and Poly I:C RNA

Non-Viral Delivery and Therapeutic Application of Small Interfering RNAs

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