siRNA nanoparticles: the future of RNAi therapeutics for oncology?

  title={siRNA nanoparticles: the future of RNAi therapeutics for oncology?},
  author={Szu-Ting Chou and A James Mixson},
  volume={9 15},
siRNA clinical trials: state of the art With the emergence of siRNA-based nanomedicine as a powerful therapeutic strategy for cancers, seven of these therapeutics have now advanced to clinical trials. Carriers of siRNA therapeutics include transferrin-modified cyclodextrin (CALAA-01, Arrowhead Research Corporation, CA, USA), in vivo jetPEI (SNS01-T; Sevion Technologies, NJ, USA), cationic liposomes (ALN-VSP02, Alnylam Pharmaceuticals, MA, USA; TKM080301, Tekmira Pharmaceuticals, Burnaby, Canada… 
Targeting siRNAs in cancer drug delivery
Systemic Delivery of Folate-PEG siRNA Lipopolyplexes with Enhanced Intracellular Stability for In Vivo Gene Silencing in Leukemia.
Protection of small interfering RNA (siRNA) against degradation and targeted delivery across the plasma and endosomal membranes to the final site of RNA interference (RNAi) are major aims for the
Co-delivery of pretubulysin and siEG5 to EGFR overexpressing carcinoma cells.
Advanced Strategies in Immune Modulation of Cancer Using Lipid-Based Nanoparticles
The use of nanoparticle-based system for immunotherapy is a promising strategy that can simultaneously target multiple pathways with the same kinetics to enhance antitumor response.
Variable Heavy Chain Domain Derived from a Cell-Penetrating Anti-DNA Monoclonal Antibody for the Intracellular Delivery of Biomolecules
Results indicate that the recombinant 2C10 VH domain could be applied as an efficient vehicle capable of delivering valuable biomolecule into the cytoplasm or cell nuclei for clinical uses.
Immunomodulation of hematological malignancies using oligonucleotides based-nanomedicines.
Efficient Shielding of Polyplexes Using Heterotelechelic Polysarcosines
Polysarcosine is a promising alternative for the shielding of non-viral, lipo-cationic polyplexes and showed enhanced blood circulation times in bioimaging studies compared to unshielded polyplexe and similar to PEG-shieldedpolyplexes.
1 Efficient Shielding of Polyplexes using 2 Heterotelechelic Polysarcosines 3
Polysarcosine is a promising alternative for the shielding of non-viral, lipo-cationic polyplexes and showed enhanced blood circulation times in bioimaging studies compared to unshielded 30 polyplexe and similar to PEG-shieldedpolyplexes.


Liposomal siRNA nanocarriers for cancer therapy.
Targeted polymeric micelles for siRNA treatment of experimental cancer by intravenous injection.
Stable and targeted micelles that deliver siRNA to solid tumors and elicit a therapeutic effect are described, which could potentially expand the utility of siRNA-based therapies for cancer treatments that require intravenous injection.
Therapeutic EphA2 gene targeting in vivo using neutral liposomal small interfering RNA delivery.
The feasibility of siRNA incorporated into the neutral liposome 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine (DOPC) for efficient in vivo siRNA delivery and DOPC-encapsulated siRNA targeting the oncoprotein EphA2 was highly effective in reducing in vivo Eph a2 expression 48 hours after a single dose are shown.
A double-modulation strategy in cancer treatment with a chemotherapeutic agent and siRNA.
A novel double modulation strategy in cancer treatment is proposed, in which chemotherapy enhances intratumoral siRNA delivery and the delivered siRNA enhances the chemosensitivity of tumors.
Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles
Evidence is provided of inducing an RNAi mechanism of action in a human from the delivered siRNA and the presence of an mRNA fragment that demonstrates that siRNA-mediated mRNA cleavage occurs specifically at the site predicted for anRNAi mechanism from a patient who received the highest dose of the nanoparticles.
Stable RNA nanoparticles as potential new generation drugs for cancer therapy.
Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy
Recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges are discussed.
Lipid-like materials for low-dose, in vivo gene silencing
A formulation has been identified that enables siRNA-directed liver gene silencing in mice at doses below 0.01 mg/kg and was shown to specifically inhibit expression of five hepatic genes simultaneously, after a single injection.
Enhancing tumor cell response to chemotherapy through nanoparticle-mediated codelivery of siRNA and cisplatin prodrug
A versatile nanoparticle (NP) platform to deliver a cisplatin prodrug and REV1/REV3L-specific siRNAs simultaneously to the same tumor cells and demonstrates the potency of the siRNA-containing NPs to knock down target genes efficiently both in vitro and in vivo.
Delivery materials for siRNA therapeutics.
An introduction to the biological challenges that siRNA delivery materials aim to overcome is provided, as well as a discussion of the way that the most effective and clinically advanced classes of si RNA delivery systems are designed to surmount these challenges.