PEI-NIR Heptamethine Cyanine Nanotheranostics for Tumor Targeted Gene DeliveryClick to copy article linkArticle link copied!
- Eduardo De los Reyes-BerbelEduardo De los Reyes-BerbelDepartment of Organic Chemistry, Biotechnology Institute, Faculty of Sciences, University of Granada, 18071 Granada, SpainMore by Eduardo De los Reyes-Berbel
- Rafael Salto-GonzalezRafael Salto-GonzalezDepartment of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, SpainMore by Rafael Salto-Gonzalez
- Mariano Ortega-MuñozMariano Ortega-MuñozDepartment of Organic Chemistry, Biotechnology Institute, Faculty of Sciences, University of Granada, 18071 Granada, SpainMore by Mariano Ortega-Muñoz
- Francisco Jose Reche-PerezFrancisco Jose Reche-PerezDepartment of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, SpainMore by Francisco Jose Reche-Perez
- Ana Belen Jodar-ReyesAna Belen Jodar-ReyesBiocolloid and Fluid Physics Group, Department of Applied Physics, Faculty of Sciences, University of Granada, 18071 Granada, SpainMore by Ana Belen Jodar-Reyes
- Fernando Hernandez-MateoFernando Hernandez-MateoDepartment of Organic Chemistry, Biotechnology Institute, Faculty of Sciences, University of Granada, 18071 Granada, SpainMore by Fernando Hernandez-Mateo
- Maria Dolores Giron-Gonzalez*Maria Dolores Giron-Gonzalez*E-mail: [email protected]Department of Biochemistry and Molecular Biology II, School of Pharmacy, University of Granada, 18071 Granada, SpainMore by Maria Dolores Giron-Gonzalez
- Francisco Santoyo-Gonzalez*Francisco Santoyo-Gonzalez*E-mail: [email protected]Department of Organic Chemistry, Biotechnology Institute, Faculty of Sciences, University of Granada, 18071 Granada, SpainMore by Francisco Santoyo-Gonzalez
Abstract
Polymer-based nanotheranostics are appealing tools for cancer treatment and diagnosis in the fast-growing field of nanomedicine. A 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 is reported. Branched PEI-2 kDa (b2kPEI) is conjugated with IR-780 and IR-783 dyes by both covalent and noncovalent simple preparative methodologies varying their stoichiometry ratio. The as-prepared set of PEI-NIR-HC nanocarriers are assayed in vitro and 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 with concomitant 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 diagnostics, avoiding additional incorporation of additional tumor-specific targeting bioligands.
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