posted on 2015-10-14, 00:00authored byYiliu Liu, Thomas Pauloehrl, Stanislav I. Presolski, Lorenzo Albertazzi, Anja R. A. Palmans, E. W. Meijer
Single-chain polymeric
nanoparticles (SCPNs) are intriguing systems
for multiple applications. In order to arrive at a controlled, but
random, positioning of the different side groups to the polymer backbone,
alternative synthetic routes have to be developed. Here, a general
postpolymerization modification strategy of poly(pentafluorophenyl
acrylate) (pPFPA) is presented as a versatile method to rapidly access
functional SCPNs. We first show that the sequential addition of a
benzene-1,3,5-tricarboxamide-based amine, acting as the supramolecular
recognition motif, and water-soluble polyetheramine (Jeffamine) to
pPFPA affords random copolymers that fold in water into SCPNs. The
scope of the modular platform is illustrated by preparing two types
of functional SCPNs. First, we prepared SCPNs designed for bio-orthogonal
catalysis by attaching pendant mono(benzimidazoylmethyl)-bis(pyridylmethyl)
(Bimpy), phenanthroline (Phen), or 2,2′-bipyridine (BiPy),
ligands capable of binding either Cu(I) or Pd(II). The Bimpy- and
Phen-containing SCPNs ligated to Cu(I) significantly accelerate azide–alkyne
cycloaddition reactions while Bipy-containing SCPNs ligated to Pd(II)
efficiently catalyze depropargylation reactions. In all cases, reactions
proceeded efficiently in phosphate buffer at a physiological pH and
at low substrate concentrations. Next, the potential of SCPNs for
photodynamic therapy was evaluated. Introducing porphyrins in SCPNs
leads to novel photosensitizers that can produce singlet oxygen (1O2) upon photoirradiation. Additionally, by attaching
both porphyrins and prodrug models, attached via 1O2-cleavable amino-acrylate linker, to the SCPNs, we show that
irradiation of the SCPNs results in a cascade reaction of 1O2 generation followed by cleavage of the amino-acrylate
linkers, releasing the drug model. The modular synthesis strategy
reported here provides rapid and controlled access to SCPNs with tunable
amounts of active units that fulfill different functions.