Magnetic Responsive Release of Nitric Oxide from an MOF-Derived Fe<sub>3</sub>O<sub>4</sub>@PLGA Microsphere for the Treatment of Bacteria-Infected Cutaneous Wound
Chieh-Wei Chung, Bo-Wen Liao, Shu-Wei Huang, Show-Jen Chiou, Cheng-Han Chang, Sheng‐Ju Lin, Bo‐Hao Chen, Wei-Ling Liu, Shang‐Hsiu Hu, Yu‐Chun Chuang, Chia‐Her Lin, I‐Jui Hsu, Chao‐Min Cheng, Chieh‐Cheng Huang, Tsai‐Te Lu
Abstract
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.