Synthesis of Highly Functionalized Poly(alkyl cyanoacrylate) Nanoparticles by Means of Click Chemistry

Abstract

A general methodology was proposed to prepare highly functionalized poly(alkyl cyanoacrylate) nanoparticles by means of Huisgen 1,3-dipolar cyclo-addition, the so-called click chemistry. To achieve this goal, different protocols were investigated to obtain azidopoly(ethylene glycol) cyanoacetate of variable molar mass, followed by a Knoevenagel condensation-Michael addition reaction with hexadecyl cyanoacetate to produce a poly[(hexadecyl cyanoacrylate)-co-azidopoly(ethylene glycol) cyanoacrylate] (P(HDCA-co-N 3 PEGCA)) copolymer, displaying azide functionalities at the extremity of the PEG chains. As a proof of concept, model alkynes were quantitatively coupled either to the P(HDCA-co-N 3 PEGCA) copolymers in homogeneous medium followed by self-assembly in aqueous solution or directly at the surface of the preformed P(HDCA-co-N 3 PEGCA) nanoparticles in aqueous dispersed medium, both yielding highly functionalized nanoparticles. This versatile approach, using alkyl cyanoacrylate derivatives, opened the door to ligand-functionalized and biodegradable nanoparticles with "stealth" properties for biomedical applications.

Polycyanoacrylates

“…Such PEGylated nanoparticles have been loaded with fluorescent quantum dots for in vitro and in vivo bioimaging (164), and with anticancer drugs for delivery to the brain (160). Click chemistry techniques have also been used to prepare highly surface functionalised PACA nanoparticles (165). Recent milestone publications have reported the use of Click chemistry for the efficient surface functionalization of polymeric nanoparticles and their use to successfully target cancer and Alzheimer's disease.…”

“Click” Conjugation of Peptide on the Surface of Polymeric Nanoparticles for Targeting Tumor Angiogenesis

“…To achieve the conjugation of CBO-P11 to PVDF-g-PAA nanoparticles without modifying the bioactivity of targeting peptide, we investigated "click" reaction, which has received much attention for preparation of bioconjugated systems due to its high degree of selectivity and stability and its potential use under physiological aqueous conditions (20)(21)(22). We have chosen to take advantage of Huisgen 1,3-dipolar cyclo-addition to conjugate alkynepeptide and azido polymeric nanoparticles (Scheme 1).…”

Colloidal micro- and nano-particles as templates for polyelectrolyte multilayer capsules

“…For example, insulin [80] or hemoglobin can be directly loaded into particles by calcium carbonate [81,82] or manganese carbonate templating [83]. Such particles could also be suitable for biocompatible polymer coverage using the layer-by-layer (LbL) assembly approach.…”