Functionalization of Active Ester-Based Polymersomes for Enhanced Cell Uptake and Stimuli-Responsive Cargo Release.
Poly(2,3-dihydroxypropyl methacrylamide) (P(DHPMA))-based amphiphilic block copolymers have recently proven to form polymer vesicles (polymersomes). In this work, we further expand their potential by incorporating (i) units for pH-dependent disintegration into the hydrophobic membrane and (ii) mannose as targeting unit into the hydrophilic block. This last step relies on the use of an active ester prepolymer. We confirm the stability of the polymersomes against detergents like Triton X-100 and their low cytotoxicity. The incorporation of 2-(2,2-dimethyl-1,3-dioxolane-4-yl)ethyl methacrylate into the hydrophobic block (lauryl methacrylate) allows a pH-responsive disintegration for cargo release. Efficient decomposition of the polymersome structure is monitored by dynamic light scattering. It is thus possible to include an active enzyme (glucose oxidase), which gets only active (is set free) after vesicle disintegration. In addition, the introduction of mannose as targeting structure allows enhanced and selective targeting of dendritic cells.
Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.
Martin
M
Scherer
Department of Dermatology, University Medical Center, Johannes Gutenberg-University Mainz , Obere Zahlbacher Straße 63, 55131 Mainz, Germany.
Cinja
C
Kappel
Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.
Nicole
N
Mohr
Institute of Physical Chemistry, Johannes Gutenberg University Mainz , Jakob-Welder-Weg 11, 55099 Mainz, Germany.
Karl
K
Fischer
Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.
Philipp
P
Heller
Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.
Romina
R
Forst
Institute of Zoology, Johannes Gutenberg University Mainz , J.-J.-Becher-Weg 7, 55128 Mainz, Germany.
Frank
F
Depoix
Department of Dermatology, University Medical Center, Johannes Gutenberg-University Mainz , Obere Zahlbacher Straße 63, 55131 Mainz, Germany.
Matthias
M
Bros
Institute of Organic Chemistry, Johannes Gutenberg-University Mainz , Duesbergweg 10-14, 55128 Mainz, Germany.
Rudolf
R
Zentel
D004148:Dioxolanes / Q000737:chemistry; D016503:Drug Delivery Systems; D004952:Esters / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions / Q000187:drug effects; D008689:Methacrylates / Q000138:chemical synthesis / Q000737:chemistry*; D017830:Octoxynol / Q000737:chemistry; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*
D004148:Dioxolanes; D004952:Esters; D008689:Methacrylates; D011108:Polymers; C115846:dodecyl methacrylate; D017830:Octoxynol; C010962:formal glycol