A ⁸⁹Zr-labeled lipoplex nanosystem for image-guided gene delivery: design, evaluation of stability and in vivo behavior

Journal Article · Mon Jan 01 00:00:00 EST 2018 · International Journal of Nanomedicine

DOI:https://doi.org/10.2147/ijn.s179806· OSTI ID:1627995

Hajdu, Istvan ^[1]; Makhlouf, Amal ^[2]; Solomon, Viswas Raja  ^[3]; Michel, Deborah  ^[1]; Al-Dulaymi, Mays ^[1]; Wasan, Kishor M. ^[1]; Fonge, Humphrey  ^[4]; Badea, Ildiko ^[1]

---

1. Univ. of Saskatchewan, Saskatoon, SK (Canada). Drug Discovery and Development Research Group, College of Pharmacy and Nutrition
2. Univ. of Saskatchewan, Saskatoon, SK (Canada). Drug Discovery and Development Research Group, College of Pharmacy and Nutrition; Cairo Univ. (Egypt). Dept. of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy
3. Univ. of Saskatchewan, Saskatoon, SK (Canada). Department of Medical Imaging, College of Medicine
4. Univ. of Saskatchewan, Saskatoon, SK (Canada). Department of Medical Imaging, College of Medicine; Royal Univ. Hospital, Saskatoon (Canada). Dept. of Medical Imaging

Background: With the advances in radiopharmaceutical research, the development of image-guided therapy has become a major interest. While the development of theranostic nanotherapeutics is frequently associated with cancer chemotherapy, phototherapy and radiotherapy, there is little information available on the in vivo monitoring of gene delivery systems and the application of image-guided approach in gene therapy. The goal of this work was to determine the in vivo behavior of DNA delivery nanosystems - based on cationic gemini surfactants – designed for image-guided gene therapy. We tested the feasibility of monitoring tumor accumulation of gene delivery nanoparticles by positron emission tomography. Methods: To be able to conjugate radiotracers to the nanoparticles, a deferoxamine-modified gemini surfactant was synthesized, DNA-containing lipoplex nanoparticles were formulated, and radiolabeled with Zirconium-89 (⁸⁹Zr). The pharmacokinetics and biodistribution of ⁸⁹Zr labeled surfactant and ⁸⁹Zr labeled nanoparticles were monitored in mice by microPET/CT imaging and ex vivo gamma counting. Results: Modification of the nanoparticles with deferoxamine did not alter their physicochemical properties. The radiolabeled nanoparticles (labeling efficiency of 95±3%) were stable in PBS and serum. The biological half-life of the 89Zr labeled nanoparticles was significantly higher compared to 89Zr labeled surfactant. As expected, the nanoparticles had significantly higher liver accumulation than the radiolabeled surfactant alone and lower kidney accumulation. Tumor uptake was detected at 2 hours post injection and decreased throughout the 3-day monitoring. Conclusion: We propose that radiolabeling DNA delivery lipoplex nanosystems is a promising approach for the design and optimization of image-guided nanomedicines, especially in the context of cancer gene therapy.

• Research Organization: SLAC National Accelerator Lab., Menlo Park, CA (United States)
• Sponsoring Organization: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)
• Grant/Contract Number: AC02-76SF00515; P41GM103393
• OSTI ID: 1627995
• Journal Information: International Journal of Nanomedicine, Vol. Volume 13; ISSN 1178-2013
• Publisher: Dovepress
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
Science & Technology - Other Topics
Pharmacology & Pharmacy
gemini surfactant
pharmacokinetic
biodistribution
melanoma
microPET imaging