title: Nanoscale Biodegradable Organic-Inorganic Hybrids for Efficient Cell Penetration and Drug Delivery.
abstract: We report a comprehensive study on novel, highly efficient, and biodegradable hybrid molecular transporters. To this end, we designed a series of cell-penetrating, cube-octameric silsesquioxanes (COSS), and investigated cellular uptake by confocal microscopy and flow cytometry. A COSS with dense spatial arrangement of guanidinium groups displayed fast uptake kinetics and cell permeation at nanomolar concentrations in living HeLa cells. Efficient uptake was also observed in bacteria, yeasts, and archaea. The COSS-based carrier was significantly more potent than cell-penetrating peptides (CPPs) and displayed low toxicity. It efficiently delivered a covalently attached cytotoxic drug, doxorubicin, to living tumor cells. As the uptake of fluorescently labeled carrier remained in the presence of serum, the system could be considered particularly attractive for the in vivo delivery of therapeutics.
authors: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.
authors: Sebastian
authors: S
authors: Hörner
authors: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.
authors: Sascha
authors: S
authors: Knauer
authors: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.
authors: Christina
authors: C
authors: Uth
authors: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.
authors: Marina
authors: M
authors: Jöst
authors: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 16, 64287, Darmstadt, Germany.
authors: Volker
authors: V
authors: Schmidts
authors: Institut für Organische und Biomolekulare Chemie, Georg-August Universität Göttingen, Tammannstrasse 2, 37077, Göttingen, Germany.
authors: Holm
authors: H
authors: Frauendorf
authors: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 16, 64287, Darmstadt, Germany.
authors: Christina Marie
authors: CM
authors: Thiele
authors: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.
authors: Olga
authors: O
authors: Avrutina
authors: Clemens-Schöpf-Institut für Organische Chemie und Biochemie, Technische Universität Darmstadt, Alarich-Weiss-Strasse 4, 64287, Darmstadt, Germany.
authors: Harald
authors: H
authors: Kolmar
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D015394:Molecular Structure; D017646:Organosilicon Compounds / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D017646:Organosilicon Compounds; D004317:Doxorubicin
keywords: COSS; cell penetration; cell-penetrating compound; drug delivery; silsesquioxanes