Polymer Nanoreactors with Dual Functionality: Simultaneous Detoxification of Peroxynitrite and Oxygen Transport

Abstract

The design of multifunctional systems is in focus today as a key strategy for coping with complex challenges in various domains that include chemistry, medicine, environmental sciences, and technology. Herein, we introduce protein-containing polymer nanoreactors with dual functionality: peroxynitrite degradation and oxygen transport. Vesicles made of poly-(2-methyloxazoline)-poly(dimethylsiloxane)-poly(2-methyloxazoline) successfully encapsulated hemoglobin (Hb), which serves as a model protein because of its dual function in oxygen transport and peroxynitrite degradation. By inserting channel proteins, the polymer membranes of vesicles permitted passage of various compounds that served for the assessment of in situ Hb activity. The requisite conformational changes in the protein structure and the change in oxidation states that took place within the confined space of the vesicle cavity demonstrated that Hb preserved its dual functionality: peroxynitrite degradation and oxygen transport. The functionality of our nanoreactor, combined with its simple procedure of production and extensive stability over several months, supports it as a promising system for further medical applications.

Artificial Organelles: Reactions inside Protein–Polymer Supramolecular Assemblies

“…[24] Interestingly, by encapsulating enzymes with dual-functions, such as haemoglobin, it was possible to design multifunctional nanoreactors to simultaneously transport oxygen and degrade peroxynitrites. [25] Reactions inside nanocompartments should be chosen to effectively meet the challenges of the desired applications. For example, in the case of oxidative stress involving reactive oxygen species in high levels that can damage cells, it is essential to decrease their intracellular concentration.…”

Interfacing Functional Systems

“…[3,19,23,[25][26][27][28] The interfacing of pores in polymersomes and liposomes with enzymes and synthetic catalysts leads to tertiary systems 15-17. [3,29,30] Such tertiary systems may interface with themselves to yield quaternary systems 18 or with cells in an analogue manner to yield simple artificial organelles. [29] In a next round of interfacing, the pores or membrane proteins in a nanoreactor can be genetically/chemically modified to trigger in situ reactions or possibly release the cargo 'on demand'.…”

“…[3,29,30] Such tertiary systems may interface with themselves to yield quaternary systems 18 or with cells in an analogue manner to yield simple artificial organelles. [29] In a next round of interfacing, the pores or membrane proteins in a nanoreactor can be genetically/chemically modified to trigger in situ reactions or possibly release the cargo 'on demand'. OmpF, a bacterial porin, was chemically modified to accept a hydrazine to yield a hydrazone bound fluorophore, which blocked the pore.…”

Protein–Polymer Supramolecular Assemblies: A Key Combination for Multifunctionality

“…[24] A variety of nanoreactors have been reported as a result of changing the active compounds, and therefore the intended applications. [22][23][24][25] For example, we introduced the concept of antioxidant nanoreactors to combat reactive oxygen species, such as superoxide radicals [23] and peroxinitrites, [26] which are well known to be involved in pathologies associated with oxidative stress. By encapsulating superoxide dismutase or its mimics inside the cavity of PMOXA-b-PDMSb-PMOXA vesicles, the active compounds detoxified superoxide radicals in situ.…”

“…[26] Indeed, hemoglobin preserved its dual activity and provided multifunctionality to the nanoreactors, when encapsulated in polymer vesicles having a membrane rendered permeable by insertion of channel porins, OmpF. The insertion of channel proteins such as OmpF represents an elegant approach for the design of nanoreactors with membrane permeable to substrates/products, which allows in situ Here we will present hybrid systems based on combining bioactive molecules (enzymes, proteins, mimics) with polymer membranes that serve as stable boundaries for nanocompartments and as bilayers on solid supports.…”