title: pHLIP peptide targets nanogold particles to tumors.
abstract: Progress in nanomedicine depends on the development of nanomaterials and targeted delivery methods. In this work, we describe a method for the preferential targeting of gold nanoparticles to a tumor in a mouse model. The method is based on the use of the pH Low Insertion Peptide (pHLIP), which targets various imaging agents to acidic tumors. We compare tumor targeting by nonfunctionalized nanogold particles with nanogold-pHLIP conjugates, where nanogold is covalently attached to the N terminus of pHLIP. Our most important finding is that both intratumoral and i.v. administration demonstrated a significant enhancement of tumor uptake of gold nanoparticles conjugated with pHLIP. Statistically significant reduction of gold accumulation was observed in acidic tumors and kidney when pH-insensitive K-pHLIP was used as a vehicle, suggesting an important role of pH in the pHLIP-mediated targeting of gold nanoparticles. The pHLIP technology can substantially improve the delivery of gold nanoparticles to tumors by providing specificity of targeting, enhancing local concentration in tumors, and distributing nanoparticles throughout the entire tumor mass where they remain for an extended period (several days), which is beneficial for radiation oncology and imaging.
authors.affiliation: Physics Department, University of Rhode Island, Kingston, RI 02881, USA.
authors.forename: Lan
authors.initials: L
authors.lastname: Yao
authors.forename: Jennifer
authors.initials: J
authors.lastname: Daniels
authors.forename: Jennifer
authors.initials: J
authors.lastname: Danniels
authors.forename: Anna
authors.initials: A
authors.lastname: Moshnikova
authors.forename: Sergey
authors.initials: S
authors.lastname: Kuznetsov
authors.forename: Aftab
authors.initials: A
authors.lastname: Ahmed
authors.forename: Donald M
authors.initials: DM
authors.lastname: Engelman
authors.forename: Yana K
authors.initials: YK
authors.lastname: Reshetnyak
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Andreev
mesh_terms: D000818:Animals; D002942:Circular Dichroism; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006046:Gold; D006367:HeLa Cells; D006652:Histological Techniques; D006801:Humans; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000378:metabolism; D053768:Metal Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D050997:Nanomedicine / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy*; D016622:Silver Staining
chemical_list: D008565:Membrane Proteins; C533201:pHLIP protein; D006046:Gold