Targeted Nanoparticle‐Mediated Gene Therapy Mimics Oncolytic Virus for Effective Melanoma Treatment

Oncolytic virus has potential applications in cancer therapy. However, its clinical application is restricted by the virus‐associated biosafety issues. Here, inspired by the key role of vesicular stomatitis virus matrix protein (VSVMP) in the oncolytic vesicular stomatitis virus (VSV) induced apoptosis, a targeted nanoparticle‐delivered neutral VSVMP gene formulation is designed to act like the VSV for cancer therapy. This VSVMP formulation consists of a CRGDKGPDC peptide modified hybrid monomethoxy poly (ethylene glycol)‐poly(d,l‐lactide) nanoparticles complexed with VSVMP plasmid, having good blood compatibility and tumor targeting ability. The transfection efficiency is as high as that of VSV. After intravenous administration, the VSVMP formulation can efficiently target the tumor, significantly inhibit the melanoma growth and metastasis, prolong the survival time of tumor‐bearing mice, and does not cause obvious systemic toxicity. The anticancer mechanisms involve apoptosis induction, angiogenesis inhibition and some virus‐associated signal pathways activation. This work demonstrates a VSV‐inspired nonviral gene therapy that has promising clinical applications in melanoma treatment.

[1]  J. Pober,et al.  Nanoparticle targeting to the endothelium during normothermic machine perfusion of human kidneys , 2017, Science Translational Medicine.

[2]  M. Kay,et al.  Rescue of Pompe disease in mice by AAV-mediated liver delivery of secretable acid α-glucosidase , 2017, Science Translational Medicine.

[3]  Shoufang Gong,et al.  Short DNA Hairpins Compromise Recombinant Adeno-Associated Virus Genome Homogeneity. , 2017, Molecular therapy : the journal of the American Society of Gene Therapy.

[4]  W. Tan,et al.  Multifunctional Molecular Beacon Micelles for Intracellular mRNA Imaging and Synergistic Therapy in Multidrug‐Resistant Cancer Cells , 2017, Advanced functional materials.

[5]  Yonggui Fu,et al.  The role of alternative polyadenylation in the antiviral innate immune response , 2017, Nature Communications.

[6]  Abolfazl Akbarzadeh,et al.  Recent advances on liposomal nanoparticles: synthesis, characterization and biomedical applications , 2017, Artificial cells, nanomedicine, and biotechnology.

[7]  Forrest M Kievit,et al.  Nanoparticles for cancer gene therapy: Recent advances, challenges, and strategies. , 2016, Pharmacological research.

[8]  C. Thaxton,et al.  Properties of Native High‐Density Lipoproteins Inspire Synthesis of Actively Targeted In Vivo siRNA Delivery Vehicles , 2016, Advanced functional materials.

[9]  Nuria Oliva,et al.  Local triple-combination therapy results in tumour regression and prevents recurrence in a colon cancer model. , 2016, Nature materials.

[10]  S. Russell,et al.  Immunovirotherapy with vesicular stomatitis virus and PD-L1 blockade enhances therapeutic outcome in murine acute myeloid leukemia. , 2016, Blood.

[11]  J. S. Suk,et al.  Biodegradable DNA Nanoparticles that Provide Widespread Gene Delivery in the Brain. , 2016, Small.

[12]  Luigi Naldini,et al.  Gene therapy returns to centre stage , 2015, Nature.

[13]  N. Artzi,et al.  Bioresponsive antisense DNA gold nanobeacons as a hybrid in vivo theranostics platform for the inhibition of cancer cells and metastasis , 2015, Scientific Reports.

[14]  H. Byrne,et al.  Dual Targeted Immunotherapy via In Vivo Delivery of Biohybrid RNAi‐Peptide Nanoparticles to Tumor‐Associated Macrophages and Cancer Cells , 2015, Advanced functional materials.

[15]  J. S. Suk,et al.  Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy , 2015, Proceedings of the National Academy of Sciences.

[16]  Wei Wang,et al.  Cationic nanocarriers induce cell necrosis through impairment of Na+/K+-ATPase and cause subsequent inflammatory response , 2015, Cell Research.

[17]  D. Schadendorf,et al.  Nivolumab in previously untreated melanoma without BRAF mutation. , 2015, The New England journal of medicine.

[18]  Dong Soo Yun,et al.  Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature. , 2014, Nano letters.

[19]  Chun-Wen Hsiao,et al.  Enhancement of efficiency of chitosan-based complexes for gene transfection with poly(γ-glutamic acid) by augmenting their cellular uptake and intracellular unpackage. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[20]  N. McMillan,et al.  Gene delivery: cell-specific therapy on target. , 2014, Nature nanotechnology.

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

[22]  U. Dietrich,et al.  Re-engineering vesicular stomatitis virus to abrogate neurotoxicity, circumvent humoral immunity, and enhance oncolytic potency. , 2014, Cancer research.

[23]  Robert Langer,et al.  Degradable Lipid Nanoparticles with Predictable In Vivo siRNA Delivery Activity , 2014, Nature Communications.

[24]  Daniel G. Anderson,et al.  In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight. , 2014, Nature nanotechnology.

[25]  Shi Zeng,et al.  Synthesis, Characterization, and Evaluation of a Novel Amphiphilic Polymer RGD-PEG-Chol for Target Drug Delivery System , 2014, TheScientificWorldJournal.

[26]  R. Cattaneo,et al.  New viruses for cancer therapy: meeting clinical needs , 2013, Nature Reviews Microbiology.

[27]  Chih-Kuang Chen,et al.  Overcoming nonviral gene delivery barriers: perspective and future. , 2013, Molecular pharmaceutics.

[28]  Zhiyao He,et al.  Gene delivery with active targeting to ovarian cancer cells mediated by folate receptor alpha. , 2013, Journal of biomedical nanotechnology.

[29]  Nirav R. Shah,et al.  Resistance of pancreatic cancer cells to oncolytic vesicular stomatitis virus: role of type I interferon signaling. , 2013, Virology.

[30]  K. Flaherty,et al.  From genes to drugs: targeted strategies for melanoma , 2012, Nature Reviews Cancer.

[31]  P. Huang,et al.  Current good manufacturing practice production of an oncolytic recombinant vesicular stomatitis viral vector for cancer treatment. , 2011, Human gene therapy.

[32]  Yuquan Wei,et al.  Efficient inhibition of C-26 colon carcinoma by VSVMP gene delivered by biodegradable cationic nanogel derived from polyethyleneimine. , 2010, ACS nano.

[33]  Erkki Ruoslahti,et al.  Coadministration of a Tumor-Penetrating Peptide Enhances the Efficacy of Cancer Drugs , 2010, Science.

[34]  L. Fazli,et al.  Oncolysis of prostate cancers induced by vesicular stomatitis virus in PTEN knockout mice. , 2010, Cancer research.

[35]  Erkki Ruoslahti,et al.  Tissue-penetrating delivery of compounds and nanoparticles into tumors. , 2009, Cancer cell.

[36]  W. Shi,et al.  Antitumor and antimetastatic activities of vesicular stomatitis virus matrix protein in a murine model of breast cancer , 2009, Journal of Molecular Medicine.

[37]  Meredith A Mintzer,et al.  Nonviral vectors for gene delivery. , 2009, Chemical reviews.

[38]  Xia Zhao,et al.  Vesicular stomatitis virus matrix protein gene enhances the antitumor effects of radiation via induction of apoptosis , 2008, Apoptosis.

[39]  D. Lyles,et al.  Oncolytic Vesicular Stomatitis Virus Induces Apoptosis via Signaling through PKR, Fas, and Daxx , 2006, Journal of Virology.

[40]  G. Barber,et al.  Development of Recombinant Vesicular Stomatitis Viruses That Exploit Defects in Host Defense To Augment Specific Oncolytic Activity , 2003, Journal of Virology.

[41]  Mark A. Kay,et al.  Progress and problems with the use of viral vectors for gene therapy , 2003, Nature Reviews Genetics.

[42]  M. Hashida,et al.  Effects of erythrocytes and serum proteins on lung accumulation of lipoplexes containing cholesterol or DOPE as a helper lipid in the single-pass rat lung perfusion system. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[43]  G. Levi,et al.  Rapid crossing of the pulmonary endothelial barrier by polyethylenimine/DNA complexes , 2000, Gene Therapy.