HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Nanoparticle-enabled, image-guided treatment planning of target specific RNAi therapeutics in an orthotopic prostate cancer model.

Abstract
The abilities to deliver siRNA to its intended action site and assess the delivery efficiency are challenges for current RNAi therapy, where effective siRNA delivery will join force with patient genetic profiling to achieve optimal treatment outcome. Imaging could become a critical enabler to maximize RNAi efficacy in the context of tracking siRNA delivery, rational dosimetry and treatment planning. Several imaging modalities have been used to visualize nanoparticle-based siRNA delivery but rarely did they guide treatment planning. We report a multimodal theranostic lipid-nanoparticle, HPPS(NIR)-chol-siRNA, which has a near-infrared (NIR) fluorescent core, enveloped by phospholipid monolayer, intercalated with siRNA payloads, and constrained by apoA-I mimetic peptides to give ultra-small particle size (<30 nm). Using fluorescence imaging, we demonstrated its cytosolic delivery capability for both NIR-core and dye-labeled siRNAs and its structural integrity in mice through intravenous administration, validating the usefulness of NIR-core as imaging surrogate for non-labeled therapeutic siRNAs. Next, we validated the targeting specificity of HPPS(NIR)-chol-siRNA to orthotopic tumor using sequential four-steps (in vivo, in situ, ex vivo and frozen-tissue) fluorescence imaging. The image co-registration of computed tomography and fluorescence molecular tomography enabled non-invasive assessment and treatment planning of siRNA delivery into the orthotopic tumor, achieving efficacious RNAi therapy.
AuthorsQiaoya Lin, Cheng S Jin, Huang Huang, Lili Ding, Zhihong Zhang, Juan Chen, Gang Zheng
JournalSmall (Weinheim an der Bergstrasse, Germany) (Small) Vol. 10 Issue 15 Pg. 3072-82 (Aug 13 2014) ISSN: 1613-6829 [Electronic] Germany
PMID24706435 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Chemical References
  • Liposomes
  • Nanocapsules
  • RNA, Small Interfering
Topics
  • Animals
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Monitoring (methods)
  • Gene Silencing
  • Genetic Therapy (methods)
  • Liposomes (chemistry)
  • Male
  • Mice
  • Microscopy, Fluorescence (methods)
  • Nanocapsules (chemistry, ultrastructure)
  • Particle Size
  • Prostatic Neoplasms (genetics, pathology, therapy)
  • RNA, Small Interfering (administration & dosage, genetics)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: