title: Cell-penetrating hyperbranched polyprodrug amphiphiles for synergistic reductive milieu-triggered drug release and enhanced magnetic resonance signals.
abstract: The rational design of theranostic nanoparticles exhibiting synergistic turn-on of therapeutic potency and enhanced diagnostic imaging in response to tumor milieu is critical for efficient personalized cancer chemotherapy. We herein fabricate self-reporting theranostic drug nanocarriers based on hyperbranched polyprodrug amphiphiles (hPAs) consisting of hyperbranched cores conjugated with reduction-activatable camptothecin prodrugs and magnetic resonance (MR) imaging contrast agent (Gd complex), and hydrophilic coronas functionalized with guanidine residues. Upon cellular internalization, reductive milieu-actuated release of anticancer drug in the active form, activation of therapeutic efficacy (>70-fold enhancement in cytotoxicity), and turn-on of MR imaging (∼9.6-fold increase in T1 relaxivity) were simultaneously achieved in the simulated cytosol milieu. In addition, guanidine-decorated hPAs exhibited extended blood circulation with a half-life up to ∼9.8 h and excellent tumor cell penetration potency. The hyperbranched chain topology thus provides a novel theranostic polyprodrug platform for synergistic imaging/chemotherapy and enhanced tumor uptake.
authors.affiliation: CAS Key Laboratory of Soft Matter Chemistry, Hefei National Laboratory for Physical Sciences at the Microscale, Collaborative Innovation Center of Chemistry for Energy Materials, Department of Polymer Science and Engineering, University of Science and Technology of China , Hefei, Anhui 230026, China.
authors.forename: Xianglong
authors.initials: X
authors.lastname: Hu
authors.forename: Guhuan
authors.initials: G
authors.lastname: Liu
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Xiaorui
authors.initials: X
authors.lastname: Wang
authors.forename: Shiyong
authors.initials: S
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D065546:Drug Liberation / Q000187:drug effects; D019791:Guanidine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011108:Polymers / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013501:Surface-Active Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011108:Polymers; D011355:Prodrugs; D013501:Surface-Active Agents; D019791:Guanidine