Multiply responsive protein nanoparticles are interesting for a variety of applications. Herein, we describe the synthesis of a vault nanoparticle that responds to both temperature and pH. Specifically, poly(N-isopropylacrylamide-co-acrylic acid) with a pyridyl disulfide end group was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymer had a lower critical solution temperature (LCST) of 31.9 °C at pH 5, 44.0 °C at pH 6 and above 60 °C at pH 7. The polymer was conjugated to human major vault protein (hMVP), and the resulting nanoparticle was analyzed by UV-Vis, dynamic light scattering (DLS) and electron microscopy. The data demonstrated that poly(N-isopropylacrylamide-co-acrylic acid)-vault conjugate did not respond to temperatures below 60 °C at pH 7, while the nanoparticles reversibly aggregated at pH 6. Furthermore, it was shown that the vault nanoparticle structure remained intact for at least three heat and cooling cycles. Thus, these dually responsive nanoparticles may serve as a platform for drug delivery and other applications.

Cyclic carbonate and δ-valerolactone substrates functionalized with ferrocene were synthesized via alkyne-azide "click" cycloaddition. The cyclic carbonates were polymerized using 1,8-diazabicycloundec-7-ene, 1-(3,5-bis(trifluoromethyl)phenyl)-3-cyclohexylthiourea, and benzyl alcohol. The resulting polymers were characterized by GPC, NMR spectroscopy, and cyclic voltammetry studies. It was found that polycarbonate molecular weights fall in the range of 4.1-5.2 × 103 g mol-1 with polydispersities as low as 1.26. Electrochemistry studies allowed us to identify the monomer/polymer pair with the most desirable redox potential for biological studies.