Stabilizing Alginate Confinement and Polymer Coating of CO-Releasing Molecules Supported on Iron Oxide Nanoparticles To Trigger the CO Release by Magnetic Heating

Abstract

Maghemite (Fe2O3) iron oxide nanoparticles (IONPs) were synthesized, modified with covalent surface-bound CO-releasing molecules of a tri(carbonyl)-chlorido-phenylalaninato-ruthenium(II) complex (CORM), and coated with a dextran polymer. The time- and temperature-dependent CO release from this CORM-3 analogue was followed by a myoglobin assay. A new measurement method for the myoglobin assay was developed, based on confining "water-soluble" polymer-coated Dextran500k@CORM@IONP particles in hollow spheres of nontoxic and easily prepared calcium alginate. Dropping a mixture of Dextran500k@CORM@IONP and sodium alginate into a CaCl2 solution leads to stable hollow spheres of Ca(2+) cross-linked alginate which contain the Dextran500k@CORM@IONP particles. This "alginate-method" (i) protects CORM-3 analogues from rapid CO-displacement reactions with a protein, (ii) enables a spatial separation of the CORM from its surrounding myoglobin assay with the alginate acting as a CO-permeable membrane, and (iii) allows the use of substances with high absorptivity (such as iron oxide nanoparticles) in the myoglobin assay without interference in the optical path of the UV cell. Embedding the CORM@IONP nanoparticles in the alginate vessel represents a compartmentation of the reactive component and allows for close contact with, yet facile separation from, the surrounding myoglobin assay. The half-life of the CO release from Dextran500k@CORM@IONP particles surrounded by alginate was determined to be 890 ± 70 min at 20 °C. An acceleration of the CO release occurs at higher temperature with a half-life of 172 ± 27 min at 37 °C and 45 ± 7 min at 50 °C. The CO release can be triggered in an alternating current magnetic field (31.7 kA m(-1), 247 kHz, 39.9 mT) through local magnetic heating of the susceptible iron oxide nanoparticles. With magnetic heating at 20 °C in the bulk solution, the half-life of CO release from Dextran500k@CORM@IONP particles decreased to 155 ± 18 min without a noticeable temperature increase in the dispersion. At 37 and 50 °C, the half-life for the CO release triggered by local magnetic heating was 65 ± 5 min and 30 ± 3 min, respectively. Thus, at a physiological temperature of 37 °C, magnetic heating accelerates the CO release of the IONP-bound CORM by a factor of ∼ 2.6. The activation energy for CO release from a CORM-3 analogue was determined to be EA = 78 kJ/mol.

Emerging Delivery Strategies of Carbon Monoxide for Therapeutic Applications: from CO Gas to CO Releasing Nanomaterials

“…Notably, as another noninvasive stimulus, heat has also shown to be a promising exogenous trigger for CO delivery. Generally, the thermal‐responsive CORMs were integrated into nanocarriers with the capacity of photon‐to‐heat or magnetic field‐to‐heat conversion in order to modulate the responsiveness of CO release and improve the bioavailability of CORMs . This will be discussed in detail in the next section.…”

“…The intrinsic magnetic‐responsive property of IONPs enables them to be employed as transporters for magnetic field‐assisted drug release and as magnetic resonance imaging (MRI) contrast agent for MRI imaging . Janiak and co‐workers first came up with a new envisioning of covalently conjugating thermal‐sensitive CORM to magnetic‐responsive IONPs (CORM@IONP) . Indeed, IONPs could act as carriers to guide CORMs to the desired position and a magnetism‐to‐heat energy converter to accelerate the thermal decomposition release of CO …”

CO-releasing molecule (CORM) conjugate systems

“…20). 66 In order to achieve water solubility, CORM@IONPs were coated with different polymers, e.g., dextrans. Using a 500 kDa dextran resulted in core-shell structures.…”

Metal-free carbon monoxide-releasing micelles undergo tandem photochemical reactions for cutaneous wound healing

“…Following the seminal work of Motterlini and coworkers, [4][5][6] a variety of CORMs have been successfully exploited. [7][8][9][10] These CORMs can be roughly categorized into two sorts, namely metal carbonyls and metal-free CORMs. Although metal carbonyls hold great promise in both laboratory and clinical investigations, 9,[11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] the development of metal-free CORMs has recently been receiveing increasing attention.…”