Superparamagnetic iron oxide-gold nanoparticles conjugated with porous coordination cages: Towards controlled drug release for non-invasive neuroregeneration

Abstract

This paper reports a smart intracellular nanocarrier for sustainable and controlled drug release in non-invasive neuroregeneration. The nanocarrier is composed by superparamagnetic iron oxide-gold (SPIO-Au) core-shell nanoparticles (NPs) conjugated with porous coordination cages (PCCs) through the thiol-containing molecules as bridges. The negatively charged PCC-2 and positively charged PCC-3 are compared for intracellular targeting. Both types result in intracellular targeting via direct penetration across cellular membranes. However, the pyrene (Py)-PEG-SH bridge enabled functionalization of SPIO-Au NPs with PCC-3 exhibits higher interaction with PC-12 neuron-like cells, compared with the rhodamine B (RhB)-PEG-SH bridge enabled case and the stand-alone SPIO-Au NPs. With neglectable toxicities to PC-12 cells, the proposed SPIO-Au-RhB(Py)-PCC-2(3) nanocarriers exhibit effective drug loading capacity of retinoic acid (RA) at 13.505 μg/mg of RA/NPs within 24 h. A controlled release of RA is achieved by using a low-intensity 525 nm LED light (100% compared to 40% for control group within 96 h).

Keywords: Intracellular targeting; Non-invasive neuroregeneration; Porous coordination cages; Superparamagnetic iron oxide-gold nanoparticles; Sustainable and controlled drug release.

Figure 1.

Schematic illustration of the nanocarrier.

Figure 2.

The TEM images of the NPs. (A) SPIO NPs (11.7 ± 1.7 nm); (B) SPIO-Au NPs (19.6 ± 3.7 nm).

Figure 3.

Light absorbance and fluorescence measurement: (A) The normalized UV-Vis spectra of the stand-alone SPIO-Au NPs, the SPIO-Au NPs functionalized with RhB-PEG-SH and the stand-alone RhB-PEG-SH (The peak absorbance value as 1). (B) The fluorescence spectrum of the SPIO-Au NPs functionalized with Py-PEG-SH. (C) The intensity distribution of hydrodynamic diameters of SPIO-Au NPs before and after the RhB-PEG-SH functionalization in DI water at 25°C (D) The intensity distribution of hydrodynamic diameters SPIO-Au NPs before and after the Py-PEG-SH functionalization in DI water at 25°C.

Figure 4.

The zeta potential measurement of (A) SPIO-Au NPs with acid neutralization for acetic acid amount increased from 20 to 500 μL at the concentration of 0.175 mol/L for every 127 μg of SPIO-Au NPs. (B) SPIO-Au NPs with acid neutralization and further functionalization with Py and PCC-3 showing that the zeta potential was changed from negative to positive. (Sample 1: original SPIO-Au; Sample 2: acid washed SPIO-Au; Sample 3: acid washed SPIO-Au-Py; Sample 4: acid washed SPIO-Au-Py-PCC-3, The PH value for all the samples in DI water were around 5.47.)

Figure 5.

The TEM images showing the cellular uptake of PC-12 cells treated with (A) SPIO-Au, (B) SPIO-Au-RhB-PCC-2 and (C) SPIO-Au-Py-PCC-3 for 24 hours. (The right parts were the enlarged images of areas in the black box in (A), (B) and (C).)

Figure 6.

The relative absorbed amount of Au in PC-12 neuron-like cells treated with SPIO-Au NPs functionalized with Py-PEG-SH, RhB-PEG-SH, PCC-2 and PCC-3. Cells without NPs were used as the control group with nearly 0 Au absorption. *p < 0.05; **p < 0.01; ***p < 0.001; ****p < 0.0001 (Original data set is listed in Table S4)

Figure 7.

The cellular viability determined from flow cytometry for PC-12 neuron-like cells treated with SPIO-Au NPs with different types of functionalization. The cells without NPs were used as control group. *p < 0.05.

Figure 8.

(A)The UV-Vis light absorbance spectra of RA solution before adding SPIO-Au-Py-PCC-3 (red line) and the RA solution after removing the RA loaded SPIO-Au-Py-PCC-3 NPs(black line). (B) Accumulated release profile of RA in DMEM from SPIO-Au-Py-PCC-3 NPs.