Surface-modified gold-coated superparamagnetic iron oxide nanoparticles promoting light-controlled drug release

The main translational barrier of neuroprotective drugs such as retinoic acid (RA) is the lack of targeted delivery to the specified brain region and the short half-life. Superparamagnetic iron-oxide (SPIO) coated with solid gold (SPIO@Au) and hollow gold (SPIO@HG) nanoparticles (NPs) have shown promise as brain-specific nanocarriers for sustainable and controlled delivery of neuroprotective drugs. However, their effectiveness has been restricted by their limited loading capacity. Surface functionalization with porous coordinate cages (PCCs) as a premium drug encapsulating component through SH-PEG-Py ligands has the potential to address this issue. Still, the traditional direct exchange (DE) method often results in insufficient functionalized ligands. This paper presents the anion exchange resin (AER)-based surface modification approach that can improve the number of functionalized ligands, regulate NP surface charges, and improve the colloidal stability by facilitating the ligand exchange reactions. This, in turn, has largely enhanced the drug encapsulation capacities of SPIO@Au NPs functionalized with PCCs. The hydrodynamic diameter and zeta-potential have validated the effectiveness of AER-based functionalization of PCCs on both SPIO@Au and SPIO@HG NPs. The colloidal stability of SPIO@Au-PCC NPs exhibits a more positive surface charge (38 mV) than the DE method (-17 mV). The loading capacity of RA with SPIO@Au-PCC has increased by 2.5 times compared with the traditional DE method (32.29 vs. 13.51 mu g/mg). The 24-h release of RA has increased to 88% from 55% through a periodic 10-min stimulation using a 100-mW LASER pointer (525 nm). This enables potential light-modulated drug release on demand. Cell viability experiments confirm excellent biocompatibility with > 92.5% cell viability of 40 mu g/ml SPIO@Au and SPIO@HG NPs in PC-12 neuron-like cells for up to 5 days of incubation. The strong colloidal stability, high drug loading capacity, and controlled drug release profile suggest the potential of AER-assisted surface modification of magneto-plasmonic nanocarriers for controlled drug delivery of neuroprotective drugs.