Nitric oxide (NO) is an essential
endogenous signaling molecule
regulating multifaceted physiological functions in the (cardio)vascular,
neuronal, and immune systems. Due to the short half-life and location-/concentration-dependent
physiological function of NO, translational application of NO as a
novel therapeutic approach, however, awaits a strategy for spatiotemporal
control on the delivery of NO. Inspired by the magnetic hyperthermia
and magneto-triggered drug release featured by Fe3O4 conjugates, in this study, we aim to develop a magnetic responsive
NO-release material (MagNORM) featuring dual NO-release phases, namely,
burst and steady release, for the selective activation of NO-related
physiology and treatment of bacteria-infected cutaneous wound. After
conjugation of NO-delivery [Fe(μ-S-thioglycerol)(NO)2]2 with a metal–organic framework (MOF)-derived
porous Fe3O4@C, encapsulation of obtained conjugates
within the thermo-responsive poly(lactic-co-glycolic
acid) (PLGA) microsphere completes the assembly of MagNORM. Through
continuous/pulsatile/no application of the alternating magnetic field
(AMF) to MagNORM, moreover, burst/intermittent/slow release of NO
from MagNORM demonstrates the AMF as an ON/OFF switch for temporal
control on the delivery of NO. Under continuous application of the
AMF, in particular, burst release of NO from MagNORM triggers an effective
anti-bacterial activity against both Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli). In addition to the magneto-triggered
bactericidal effect of MagNORM against E. coli-infected cutaneous wound in mice, of importance, steady release
of NO from MagNORM without the AMF promotes the subsequent collagen
formation and wound healing in mice.