Gold Nanoparticle Approach to the Selective Delivery of Gene Silencing in Cancer—The Case for Combined Delivery?
Abstract
:1. Gene Therapy in Cancer Therapeutics
Cancer-Related Targets for Gene Silencing
2. Addressing Current Drawbacks in Gene Silencing Therapy—Focus on Nanomedicine
2.1. Nanomedicine Applied to Gene Therapy
2.2. Gold Nanoparticles Applied to Gene-Silencing Therapeutics
3. Combinatory Approaches
3.1. Gene Silencing–Gene Silencing
3.2. Gene Silencing–Chemotherapy
3.3. Gene Silencing–Light Induced Therapeutics
3.4. Gene Silencing–Radiotherapy
3.5. Gene Silencing–Immunotherapy
4. Translation to the Clinics
Acknowledgments
Conflicts of Interest
References
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Gene | RNAi Technology | Effect on Tumor Cells | Reference |
---|---|---|---|
B-cell lymphoma/leukemia 2 protein (BCL-2) (oncogene) | siRNA | Induced apoptosis in vitro | [1] |
BCL-2 (oncogene) | shRNA | Suppressed tumor growth in mice with xenograft tumor | [1] |
Clusterin (CLU) (heterodimeric glycoprotein) | siRNA | Decrease in cancer cell proliferation and an increase in apoptosis rate in vitro | [1] |
CLU (heterodimeric glycoprotein) | siRNA | CLU siRNA treated MDA-MB-231 cells grew significantly slower in vivo | [1] |
N-acetylglucosaminyltransferase V (GNT-V) (overexpression in malignant tumors) | siRNA | Decreased proliferation of BGC823 cells | [1] |
Peptidyl-prolyl cis/trans isomerase (PIN1) (overexpression in prostate and breast cancers) | shRNA | Inhibited tumor growth, metastasis and angiogenesis | [1] |
Vascular Endothelial Growth Factor (VEGF) | shRNA | Inhibited cancer cell proliferation and tumor growth, and reduced tumor microvessel density (MVD) and microlymphatic vessel density (MLVD) | [1] |
Eukaryotic Initiation Factor 3 c (eIF3c) (oncogene) | siRNA | The survival rate of RKO colon cancer cells drastically, the cell cycle was arrested as the number of cells entering the S phase was significantly reduced, and the induction of apoptosis was prominent | [12] |
M-BCR/ABL fusion (constitutively activated) | siRNA | Killed leukemic cells with this arrangement | [5] |
K-RASv12 allele (oncogene) | siRNA | Specifically and stably inhibited the expression of the oncogenic K-RASv12 allele while leaving the wild type K-RAS intact in human tumor cells | [5,13] |
Name (Company) | Particle Type/Drug | Application/Indication | Clinical Trials. Gov (Phase) |
---|---|---|---|
TKM-080301 (Arbutus Biopharma) | Lipid particle targeting Polo-Like Kinase 1 (PLK1) for delivery of siRNA | Hepatocellular carcinoma | NCT02191878 (Ph I/II) |
siRNA-EphA2-DOPC (M.D. Anderson Cancer Center) | siRNA liposome for EPHA2 knockdown | Solid tumors | NCT01591356 (Ph I) |
PNT2258 (ProNAi Therapeutics) | Proprietary single-stranded DNAi (PNT100) encapsulated in lipid nanoparticles | Lymphomas | NCT02378038 (Ph II) NCT02226965 (Ph II) NCT01733238 (Ph II) |
BP1001 (Bio-Path Holdings) oligonucleotide | Growth Factor Receptor Bound Protein-2 (GRB-2) antisense encapsulated in neutral liposomes | Leukemia | NCT01159028 (Ph I) |
DCR-MYC (Dicerna Pharmaceuticals) | DsiRNA lipid nanoparticle for MYC oncogene silencing | Solid tumors, multiple myeloma, lymphoma, or hepatocellular carcinoma | NCT02110563 (Ph I) NCT02314052 (Ph I/II) |
Atu027 (Silence Therapeutics GmbH) | AtuRNAi® liposomal formulation for Protein Kinase N3 (PKN3) knockdown in vascular endothelium | Pancreatic cancer | NCT01808638 (Ph I/II) |
SGT-53 (SynerGene Therapeutics) | Cationic liposome with anti-transferrin receptor antibody, encapsulating Wildtype p53 sequence | Glioblastoma, solid tumors, or pancreatic cancer | NCT02354547 (Ph I) NCT00470613 (Ph I) NCT02354547 (Ph I) NCT02340156 (Ph II) |
SGT-94 (SynerGene Therapeutics) | RB94 plasmid DNA in a liposome with anti-transferrin receptor antibody | Solid tumors | NCT01517464 (Ph I) |
MRX34 (Mirna Therapeutics) | Double-stranded RNA mimic of miR-34 encapsulated in liposomes | Liver cancer | NCT01829971 (Ph I) |
TargomiRs (EnGeneIC) | Anti-EGFR bispecific antibody minicells (bacteria derived nanoparticles) with a miR-16 based microRNA payload | Mesothelioma and Non-small cell lung cancer | NCT02369198 (Ph I) |
CALAA-01 (Calando Pharmaceuticals) | Polymer (targeted)/siRNA targeting Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) | Melanoma | NCT00689065 (Ph I) |
ALN-VSP (Alnylam Pharmaceuticals) | Lipid (non-targeted)/siRNA targeting VEGFA and KSP | Solid Tumors | NCT00882180 (Ph I) NCT01158079 (Ph I) |
Atu027 PKN3 (Silence Therapeutics) | Lipid (non-targeted)/siRNA targeting PKN3 | Advanced solid tumors and metastatic pancreatic adenocarcinoma | NCT00938574 (Ph I) NCT01808638 (Ph I/II) |
TKM-PLK1 (Tekmira Pharmaceuticals) | Lipid (non-targeted)/siRNA targeting PLK1 | solid tumors, hepatocellular carcinoma, gastrointestinal neuroendocrine tumors and adrenocortical carcinoma | NCT01262235 (Ph I/II) NCT01437007 (Ph I) NCT02191878 (Ph I/II) |
siG12D LODER (Silenseed) | Biodegradable polymer matrix/siRNA targeting K-RAS | Pancreatic Ductal Adenocarcinoma and Pancreatic cancer | NCT01188785 Ph I) NCT01676259 (Ph II) |
SNS01-T (Senesco Technologies) | Polyethylenimine (non-targeted)/eIF5AK50R plasmid eIF5A siRNA | NR | NCT01435720 (Ph II) |
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Mendes, R.; Fernandes, A.R.; Baptista, P.V. Gold Nanoparticle Approach to the Selective Delivery of Gene Silencing in Cancer—The Case for Combined Delivery? Genes 2017, 8, 94. https://doi.org/10.3390/genes8030094
Mendes R, Fernandes AR, Baptista PV. Gold Nanoparticle Approach to the Selective Delivery of Gene Silencing in Cancer—The Case for Combined Delivery? Genes. 2017; 8(3):94. https://doi.org/10.3390/genes8030094
Chicago/Turabian StyleMendes, Rita, Alexandra R. Fernandes, and Pedro V. Baptista. 2017. "Gold Nanoparticle Approach to the Selective Delivery of Gene Silencing in Cancer—The Case for Combined Delivery?" Genes 8, no. 3: 94. https://doi.org/10.3390/genes8030094