Boosting Oncolytic Adenovirus Potency with Magnetic Nanoparticles and Magnetic Force

• DOI: 10.1021/mp100123t
• Publication Date: 2010-06-15T16:40:46Z
• Authors: Nittaya Tresilwised; Pimolpan Pithayan...; Olga Mykhaylyk; Per Sonne Holm; Regina Holzmüller; Martina Anton; Stefan Thalhammer; Denis Adigüzel; Markus Döblinger; Christian Plank
• Keywords: Mice, Inbred BALB C; 0303 health sciences; Mice, Nude; Xenograft Model Antitumor Assays; Adenoviridae; 3. Good health; Pancreatic Neoplasms; Blotting, Southern; Magnetics; Mice; Oncolytic Viruses; 03 medical and health sciences; Microscopy, Electron, Transmission; Drug Resistance, Neoplasm; Cell Line, Tumor; Animals; Humans; Nanoparticles; Female

Oncolytic adenoviruses rank among the most promising innovative agents in cancer therapy. We examined potential of boosting efficacy oncolytic adenovirus dl520 by associating it with magnetic nanoparticles and magnetic-field-guided infection multidrug-resistant (MDR) cells vitro upon intratumoral injection vivo. The virus was complexed self-assembly core−shell having a magnetite core about 10 nm stabilized shell containing 68 mass % lithium 3-[2-(perfluoroalkyl)ethylthio]propionate) 32 25 kDa branched polyethylenimine. Optimized binding, sufficiently stable 50% fetal calf serum, found at nanoparticle-to-virus ratios 5 fg Fe per physical particle (VP) above. As estimated from magnetophoretic mobility measurements, 3,600 to 4,500 nanocrystallites were associated particle. Ultrastructural analysis electron atomic force microscopy showed structurally intact viruses surrounded particles that occasionally bridged several particles. Viral uptake into given dose enhanced 10-fold compared nonmagnetic when infections carried out under influence field. Increased internalization resulted enhancement potency terms required for killing target (IC50 value) an 4 orders magnitude progeny formation equal input doses viruses. Furthermore, full effect developed within two days postinfection six as reference. Plotting cell viability versus internalized inherent productivity remained unchanged association nanoparticles. Hence, we conclude mechanism is mainly due improved complexes resulting potentiated formation. Upon application gradient field murine xenograft model, exhibited stronger than alone. propose this approach would be useful during vivo administration tumor-feeding blood vessels boost primary cycle tumor. For systemic application, further modification shielding retargeting whole complex entity needed.