A Crosslinked Nucleic Acid Nanogel for Effective siRNA Delivery and Antitumor Therapy.

Functional siRNAs are employed as cross-linkers to direct the self-assembly of DNA-grafted polycaprolactone (DNA-g-PCL) brushes to form spherical and nanosized hydrogels via nucleic acid hybridization in which small interfering RNAs (siRNAs) are fully embedded and protected for systemic delivery. Owing to the existence of multivalent mutual crosslinking events inside, the crosslinked nanogels with tunable size exhibit not only good thermostability, but also remarkable physiological stability that can resist the enzymatic degradation. As a novel siRNA delivery system with spherical nucleic acid (SNA) architecture, the crosslinked nanogels can assist the delivery of siRNAs into different cells without any transfection agents and achieve the gene silencing effectively both in vitro and in vivo, through which a significant inhibition of tumor growth is realized in the anticancer treatment.

[1]  Leaf Huang,et al.  Nonviral gene therapy: promises and challenges , 2000, Gene Therapy.

[2]  C. Liu,et al.  An amphiphilic dendrimer for effective delivery of small interfering RNA and gene silencing in vitro and in vivo. , 2012, Angewandte Chemie.

[3]  K. Cichutek,et al.  Cell entry targeting restricts biodistribution of replication-competent retroviruses to tumour tissue , 2008, Gene Therapy.

[4]  Shubiao Zhang,et al.  Cationic lipids and polymers mediated vectors for delivery of siRNA. , 2007, Journal of controlled release : official journal of the Controlled Release Society.

[5]  B. Zhang,et al.  Guanidinoamidized linear polyethyleneimine for gene delivery , 2015, Chinese Journal of Polymer Science.

[6]  Matthias Epple,et al.  Inorganic nanoparticles as carriers of nucleic acids into cells. , 2008, Angewandte Chemie.

[7]  W. Keller,et al.  Degradation of DNA RNA hybrids by ribonuclease H and DNA polymerases of cellular and viral origin. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[8]  H. Maeda,et al.  Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. , 2000, Journal of controlled release : official journal of the Controlled Release Society.

[9]  Sarah Crunkhorn Trial watch: Pioneering RNAi therapy shows antitumour activity in humans , 2013, Nature Reviews Drug Discovery.

[10]  H. Maeda,et al.  The EPR effect for macromolecular drug delivery to solid tumors: Improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo. , 2013, Advanced drug delivery reviews.

[11]  Daniel G. Anderson,et al.  Knocking down barriers: advances in siRNA delivery , 2009, Nature Reviews Drug Discovery.

[12]  Yinchu Ma,et al.  Optimizing the Size of Micellar Nanoparticles for Efficient siRNA Delivery , 2015 .

[13]  Chad A Mirkin,et al.  Spherical nucleic acids. , 2012, Journal of the American Chemical Society.

[14]  Warren C W Chan,et al.  The effect of nanoparticle size, shape, and surface chemistry on biological systems. , 2012, Annual review of biomedical engineering.

[15]  Cuichen Wu,et al.  Self-assembly of DNA Nanohydrogels with Controllable Size and Stimuli-Responsive Property for Targeted Gene Regulation Therapy , 2015, Journal of the American Chemical Society.

[16]  M. Epple,et al.  Anorganische Nanopartikel zum Transport von Nucleinsäuren in Zellen , 2008 .

[17]  Omid C Farokhzad,et al.  Theranostic near-infrared fluorescent nanoplatform for imaging and systemic siRNA delivery to metastatic anaplastic thyroid cancer , 2016, Proceedings of the National Academy of Sciences.

[18]  Chuan Zhang,et al.  Recent progress on DNA block copolymer , 2017 .

[19]  John J. Rossi,et al.  The promises and pitfalls of RNA-interference-based therapeutics , 2009, Nature.

[20]  J. Fréchet,et al.  Polyphosphonium polymers for siRNA delivery: an efficient and nontoxic alternative to polyammonium carriers. , 2012, Journal of the American Chemical Society.

[21]  C. Mirkin,et al.  Biodegradable DNA-Brush Block Copolymer Spherical Nucleic Acids Enable Transfection Agent-Free Intracellular Gene Regulation. , 2015, Small.

[22]  D. Descamps,et al.  Two key challenges for effective adenovirus-mediated liver gene therapy: innate immune responses and hepatocyte-specific transduction. , 2009, Current gene therapy.

[23]  Chad A. Mirkin,et al.  Intracellular Fate of Spherical Nucleic Acid Nanoparticle Conjugates , 2014, Journal of the American Chemical Society.

[24]  Chad A Mirkin,et al.  Mechanism for the endocytosis of spherical nucleic acid nanoparticle conjugates , 2013, Proceedings of the National Academy of Sciences.

[25]  Jiye Shi,et al.  Single-particle tracking and modulation of cell entry pathways of a tetrahedral DNA nanostructure in live cells. , 2014, Angewandte Chemie.

[26]  Vladimir Torchilin,et al.  Tumor delivery of macromolecular drugs based on the EPR effect. , 2011, Advanced drug delivery reviews.

[27]  K. Howard,et al.  Polycation-based nanoparticle delivery of RNAi therapeutics: adverse effects and solutions. , 2012, Advanced drug delivery reviews.

[28]  Jin-Zhi Du,et al.  Sheddable ternary nanoparticles for tumor acidity-targeted siRNA delivery. , 2012, ACS nano.

[29]  Dongsheng Liu,et al.  Rapid formation of a supramolecular polypeptide-DNA hydrogel for in situ three-dimensional multilayer bioprinting. , 2015, Angewandte Chemie.

[30]  Daniel Anderson,et al.  Delivery materials for siRNA therapeutics. , 2013, Nature materials.

[31]  Daniel G. Anderson,et al.  Molecularly Self-Assembled Nucleic Acid Nanoparticles for Targeted In Vivo siRNA Delivery , 2012, Nature nanotechnology.

[32]  Mauro Ferrari,et al.  Principles of nanoparticle design for overcoming biological barriers to drug delivery , 2015, Nature Biotechnology.

[33]  Bulent Ozpolat,et al.  Liposomal siRNA nanocarriers for cancer therapy. , 2014, Advanced drug delivery reviews.

[34]  Daniel G. Anderson,et al.  Non-viral vectors for gene-based therapy , 2014, Nature Reviews Genetics.

[35]  Fangzhou Song,et al.  Silencing of Polo-Like Kinase (Plk) 1 via siRNA Causes Inhibition of Growth and Induction of Apoptosis in Human Esophageal Cancer Cells , 2008, Oncology.