Inhibitors that target diabetes pathology-related signaling pathways have great therapeutic potential for diabetic wound healing. Metal–organic frameworks (MOFs) are increasingly popular drug delivery systems that have high loading capacity and can release their intrinsic metal ions to act as bioactive agents. In light of this, a receptor for advanced glycation end products (RAGE) inhibitor, 4-chloro-N-cyclohexyl-N-(phenylmethyl)-benzamide (FPS-ZM1), was loaded into a cobalt (Co)-based MOF (zeolitic imidazolate framework-67, ZIF-67) to fabricate FPS-ZM1 encapsulated ZIF-67 (FZ@ZIF-67) nanoparticles (NPs). As a result, FZ@ZIF-67 NPs could dually deliver Co ions and FPS-ZM1 in a controlled manner for over 14 days. Our in vitro study showed that FZ@ZIF-67 NPs not only enhanced angiogenesis by delivering Co ions but also released FPS-ZM1 to promote M2 macrophage polarization and attenuated high glucose (HG)- and/or inflammation-induced impairment of angiogenesis through RAGE inhibition. Moreover, in an in vivo study, FZ@ZIF-67 NPs markedly improved re-epithelialization, collagen deposition, neovascularization, and relieved inflammation in diabetic wounds in rats. This study not only provides a low-cost, effective, and synergistic proangiogenic bioactive agent but also demonstrates that targeting diabetes-related pathological signaling pathways is necessary to ameliorate vascularization impairment during diabetic wound healing.

The mounting threat of antibiotic-resistant bacterial infections has made it imperative to develop innovative antibacterial strategies. Here we propose a novel antibacterial nanoplatform of silver nanoparticles-decorated and mesoporous silica coated single-walled carbon nanotubes constructed via a N-[3-(trimethoxysilyl)propyl]ethylene diamine (TSD)-mediated method (SWCNTs@mSiO₂-TSD@Ag). In this system, the outer mesoporous silica shells are able to improve the dispersibility of SWCNTs, which will increase their contact area with bacteria cell walls. Meanwhile, the large number of mesopores in silica layers act as microreactors for in situ synthesis of Ag NPs with controlled small size and uniform distribution, which induces an enhanced antibacterial activity. Compared with TSD modified mesoporous silica coated single-walled carbon nanotubes (SWCNTs@mSiO₂-TSD) and commercial Ag NPs, this combination nanosystem of SWCNTs@mSiO₂-TSD@Ag exhibits much stronger antibacterial performance against multi-drug-resistant bacteria Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) in vitro through damaging the bacterial cell membranes and a fast release of silver ions. Furthermore, the in vivo rat skin infection model verifies that SWCNTs@mSiO₂-TSD@Ag have remarkably improved abilities of bacterial clearance, wound healing promoting as well as outstanding biocompatibility. Therefore, this novel nanoplatform indicates promising potentials as a safe and powerful tool for the treatment of clinical drug-resistant infections.