Electrically Responsive, Nanopatterned Surfaces for Triggered Delivery of Biologically Active Molecules into Cells

Abstract

Polyelectrolyte multilayers (PEMs) assembled layer-by-layer have emerged as functional polymer films that are both stable and capable of containing drug molecules for controlled release applications. Most of these applications concentrate on sustained release, where the concentration of the released molecules remains rather constant with time. However, high-efficiency delivery requires obtaining high local concentrations at the vicinity of the cells, which is achieved by triggered release. Here, we show that a nanopatterned PEM platform demonstrates superior properties with respect to drug retention and triggered delivery. A chemically modified block copolymer film was used as a template for the selective deposition of poly­(ethylene imine) and a charged derivative of the electroactive poly­(3,4-ethylenedioxythiophene) together with a drug molecule. This nanopatterned PEM shows the following advantages: (1) high drug loading; (2) enhanced retention of the bioactive molecule; (3) release triggered by an electrochemical stimulus; (4) high efficacy of drug delivery to cells adsorbed on the surface compared to the delivery efficacy of a similar concentration of drug to cells suspended in a solution.

Thiophene-Based Aldehyde Derivatives for Functionalizable and Adhesive Semiconducting Polymers

“…35−38 The trimer−CHO was synthesized via Suzuki coupling reaction between 2,5-dibromo-3-thiophene aldehyde (4) and EDOT boronic acid pinacol ester (5) in presence of a palladium catalyst. The coupling between the two reagents was achieved with a good yield, and the product (6) was characterized by 1 H NMR and 13 C NMR spectroscopy (Supporting Information, Section 2). The ultraviolet− visible−near-infrared (UV−vis−NIR) absorption spectrum of the trimer−CHO exhibits a very broad absorption band between 250 and 450 nm, while EDOT−CHO absorbs only below 275 nm (Supporting Information, Figure S7a).…”

“…1 H NMR (400 MHz, chloroform-d) δ 9.76 (s, 1H), 6.45 (dd, J = 49.0, 3.7 Hz, 2H), 4.59 (t, J = 4.1 Hz, 1H), 4.38−4.27 (m, 2H). 13 (6). First, 0.3 g EDOT boronic ester (5) (1.1 mmol) and 0.14 g (0.51 mmol) 2,5-dibromo-3thiophene aldehyde (4) were dissolved in THF (12 mL) in a flamedried Schlenk flask.…”

“…The introduction of functional groups allowing the preparation of more versatile materials or conferring additional properties to the existing ones is strongly desired. Up to now, this has been generally pursued starting from commercial or easily synthesized EDOT derivates, such as the chlorine- − and the hydroxy- − methyl EDOT. There are only few examples of more reactive moieties that have been attached to EDOT, such as the carboxylic acid group, which has been directly connected to the oxygenated ring. − The advantages offered by an easily functionalizable moiety have been clearly shown by several studies, for instance, in case of a carboxylic group connected on an aliphatic chain , or in case of a click reaction via azide. − The carboxylic and the amine functional groups are particularly interesting thanks to the outstanding adhesion properties they exhibit, , mainly due to their high reactivity.…”

Electrochemically Enhanced Delivery of Pemetrexed from Electroactive Hydrogels

“…Polymer-based hydrogels are popular for biomedical applications, particularly in the development of tissue scaffolds and drug delivery systems because the polymer networks are swollen with water [16,17] facilitating transport of nutrients/waste from tissue scaffolds and bioactive payloads for drug delivery systems [18,19]. The appeal is also driven by the variety of polymers available (particularly PEG [20,21]) methods for the preparation of 3D hydrogels (e.g., chemical/photochemical/in situ crosslinking) and ease with which it is possible to tailor the properties (e.g., pore size distribution, swelling ability, mechanical properties, etc.)…”

Layer‐by‐layer assembly and electrically controlled disassembly of water‐soluble Poly(3,4‐ethylenedioxythiophene) derivatives for bioelectronic interface

“…We have previously synthesized PEDOT‐SO 3 via direct C‐H arylation polymerization [ 37 ] and used it for the electrically triggered delivery of doxorubicin into the cells. [ 38 ] We were interested in studying the LBL assembly for only PEDOT derivatives that can be further used for bioapplications.…”