title: van der Waals force-induced loading of proangiogenic nanoparticles on microbubbles for enhanced neovascularization.
abstract: Nanoparticles emerged as carriers of promising diagnostic and therapeutic molecules due to their unique size, injectability, and potential to sustainably release molecular cargos. However, with local injection of particles into target tissue, the significant particle loss caused by external biomechanical forces is a great challenge yet to be resolved to date. We hypothesized that nanoparticles associated with tissue-adherent microbubbles in the form of core-shell particles due to van der Waals attractive forces would stably remain on an implanted site and significantly increase therapeutic efficacy of drug cargos. To examine this hypothesis, we used 100 nm diameter nanoparticles made of poly(lactide-co-glycolic acid) (PLGA) as a model nanoparticle and 50 μm diameter microbubbles made of poly(2-hydroxyethyl aspartamide) (PHEA) grafted with octadecyl chains, PHEA-g-C18, as a model microbubble. Simple mixing of PLGA nanoparticles and PHEA-g-C18 microbubbles resulted in the core-shell particles. Following implantation, the PHEA-g-C18 microbubbles acted as glue to minimize the displacement of PLGA nanoparticles, because of the association between the octadecyl chains on PHEA-g-C18 and the epithelium of the tissue. As a consequence, the core-shell particles prepared with Angiopoietin-1 (Ang1)-encapsulated PLGA nanoparticles significantly promoted vascularization in the implanted tissue. Overall, the results of this study provide a simple but advanced strategy for improving therapeutic efficacy of drug-carrying nanoparticles without altering their surface chemistry and potential.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA. hjkong06@illinois.edu eqin2@illinois.edu.
authors.forename: Jinrong
authors.initials: J
authors.lastname: Chen
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Lee
authors.forename: Ellen
authors.initials: E
authors.lastname: Qin
authors.forename: Sanjay
authors.initials: S
authors.lastname: Misra
authors.forename: Hyunjoon
authors.initials: H
authors.lastname: Kong
mesh_terms: D042683:Angiopoietin-1 / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry / Q000494:pharmacology; D045423:Microbubbles; D053758:Nanoparticles / Q000737:chemistry*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000737:chemistry / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D010455:Peptides; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid