Title
PEI-NIR Heptamethine Cyanine Nanotheranostics for Tumor Targeted Gene Delivery
Author
Eduardo De los Reyes-Berbel, Rafael Salto-Gonzalez, Mariano Ortega-Muñoz, Francisco Jose Reche-Perez, Ana Belén Jódar-Reyes, Fernando Hernández-Mateo, Maria Dolores Giron-Gonzalez, Francisco Santoyo-González
Year
2018
Journal
Bioconjugate Chemistry
Abstract
Polymer-based nanotheranostics for cancer treatment and diagnosis are appealing tools in the fast-growing field of nanomedicine. In this paper, we report on the straightforward preparation of novel engineered PEI-based nanotheranostics incorporating NIR fluorescence heptamethine cyanine dyes (NIRF-HC) to enable them with tumor targeted gene delivery capabilities. Branched PEI-2kDa (b2kPEI) is conjugated with IR-780 and IR-783 dyes by either covalent and non-covalent simple preparative methodologies varying their stoichiometry ratio. The as-prepared set of PEI-NIR-HC nanocarriers are essayed in vitro an in vivo to evaluate their gene transfection efficiency, cellular uptake, cytotoxicity, internalization and trafficking mechanisms, subcellular distribution and tumor specific gene delivery. The results show the validity of the approach particularly for one of the covalent IR783-b2kPEI conjugates that exhibit an enhanced tumor uptake, probably mediated by organic anion transporting peptides, and favorable intracellular transport to the nucleus. The compound behaves as an efficient nanotheranostic transfection agent in NSG mice bearing melanoma G361 xenographs resulting in adequate imaging signal and gene concentration in the targeted tumor. By this way, advanced nanotheranostics with multifunctional capabilities (gene delivery, tumor-specific targeting and NIR fluorescence imaging) are generated in which the NIRF-HC dye component accounts for simultaneous targeting and diagnostic avoiding additional incorporation of additional tumor-specific targeting bioligands.
Instrument
FP-8300
Keywords
Fluorescence, Nanostructures, Chemical stability, Medicinal