Synthesis, conjugating capacity and biocompatibility evaluation of a novel amphiphilic polynorbornene

Abstract

Polynorbornenes, prepared by the 'living' and 'controlled' ring-opening metathesis polymerization (ROMP) method, have emerged as a stimuli-sensitive new class of polymer carriers. Herein, we reported a novel amphiphilic diblock polynorbornene, PNCHO-b-PNTEG, containing active benzaldehyde units, which exhibited good conjugating capacity to amino-containing molecules (e.g., doxorubicin (DOX)) via the pH-sensitive Schiff base linkage. The copolymer and its conjugate with DOX, DOX-PNCHO-b-PNTEG, were adequately analyzed by various techniques including 1 H NMR, 13 C NMR, gel permeation chromatography, etc. Especially, the formed conjugate of DOX-PNCHO-b-PNTEG could self-assemble into near-spherical micelles with the diameter of 81 ± 10 nm, and exhibit acid-triggered DOX release behavior, and the release rate could be adjusted by changing the environmental pH value. The excellent biological safety of PNCHO-b-PNTEG was further demonstrated by the results from both in vitro toxicity evaluation to murine fibroblast cells (L-929 cells) and in vivo evaluation of acute developmental toxicity and cell death in zebrafish embryos. Hence, the present polynorbornene-based PNCHO-b-PNTEG possesses great potential application as a biocompatible polymeric carrier and could be employed to fabricate various pHsensitive conjugates.

Induced Disassembly of a Virus-like Particle under Physiological Conditions for Venom Peptide Delivery

“…An additional concern with this system pertains to the toxicity and in vivo persistence of the polynorbornene backbone produced by ROMP disassembly. Several studies have demonstrated that polynorbornenes are not cytotoxic. − However, because these macromolecules feature an all-carbon backbone, they are not readily degradable. Nevertheless, recent work has shown that doping the pool of norbornene ROMP precursors with silyl ether-based cyclic olefins results in degradable backbones with significantly improved long-term clearance profiles .…”

Design of biomaterials through direct ring-opening metathesis polymerisation of functionalised cyclic alkenes

“…DDS based on polymer micelles composed of (oxa) norbornene derivatives with OEG-modified segments as the hydrophilic shells and drug-bearing segments as the hydrophobic core have been extensively investigated, and a wide variety of drug molecules have been introduced. Examples of such drugs include birabresib, 293 bortezomib, 295,305 camptothecin, 285,288 cisplatin, 288,[306][307][308] coumarin, [309][310][311][312] DACHplatin, 250 dexamethasone, 295 doxorubicin, 261,[285][286][287][288]296,[313][314][315][316][317][318] folate, 253,254,256 isoniazid, 319,320 paclitaxel, 217,258,290,292,310,[321][322][323] piplatine, 258 pomalidomide, 295 rifampicin, 319 retinol, 320,324 and vorinostat, 246 which have all demonstrated efficacy comparable to that of the introduced agent.…”