Tumor penetration of Sub-10 nm nanoparticles: effect of dendrimer properties on their penetration in multicellular tumor spheroids

Publication date: Available online 13 July 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Jason Bugno, Michael J. Poellmann, Karol Sokolowski, Hao-jui Hsu, Dong-Hwan Kim, Seungpyo HongAbstractUltrasmall nanoparticles (NPs, <10 nm) have promise in cancer treatment, yet little is known about how NP physical properties influence penetration through solid tumors. To elucidate the role of NP size and structure, we prepared a series of sub-10 nm poly(amidoamine) (PAMAM) dendrimers and gold NPs (AuNP), and evaluated penetration in multicellular tumor spheroids (MCTS). Smaller generation 2 dendrimers (G2-NH2, 2.9 nm diameter) penetrated 2.5-fold deeper than larger G7-NH2 (8.1 nm) (P = 0.0005). Despite increased accumulation within MCTS, electrostatic cell interactions and ligand (folic acid, FA)-mediated targeting had minimal influence on penetration. NP rigidity played a minor role in penetration, with smaller rigid AuNP (2 nm) penetrating significantly more than larger AuNP (4 nm) (3-fold, P = 0.014; G2-NH2 vs. G4-NH2, 2.8-fold, P = 0.033). Our findings highlight the importance of rational NP design and provide design cues for tailored NP distributions within solid tumors.Graphical AbstractLittle is known regarding how nanoparticle (NP) physical properties influence tumor penetration. In a tumor model we evaluated sub-10 nm poly(amidoamine) dendrimers and gold NP penetration. Penetration was strictly size-dependent, within minimal influence...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research