Core vs. surface labelling of mesoporous silica nanoparticles: advancing the understanding of nanoparticle fate and design of labelling strategies

Abstract

Despite great interest in the use of silica mesoporous nanoparticles (MSNs) in drug delivery little is known on their biological fate. Positron emission tomography (PET) studies of radiolabelled MSNs face a major difficulty due to the degradation of the MSNs during circulation as it is difficult to assign activity values to either the MSNs or their degradation products. Here, a PET study is conducted using two strategies of labelling. MSNs are either radiolabelled in the core by complexation with silanols from the MSNs with ⁸⁹Zr, or on the MSN coating through attachment of ¹³¹I radiolabelled Lin-TT1 (AKRGARSTA), a homing peptide for targeting cancer tissue. Results from the biodistribution of MSNs with the two labels are compared, obtaining meanful information on the fate of MSNs. While MSNs accumulate in liver and spleen, MSN degradation products ⁸⁹Zr or silicate bearing the radioisotope, are found in the bones and probably in lungs. A partial detachment of the peptide from the surface of the MSN is also observed. This work highlights the importance of choosing an appropriate labelling strategy for nanoparticles since core or surface labelling may result in different particle biodistribution if the labelled component degrades or the label detaches.

Scheme 1. Strategies for labelling MSNs core with ⁸⁹Zr to perform PET imaging studies and tyrosine residue iodination with ¹³¹I in attached peptides to perform ex vivo gamma counting studies.

Fig. 1. (A) Representative TEM image of MSNs. Scale bar 100 nm and (B) isotherm of nitrogen adsorption of bare and aminated mesoporous nanoparticles. The inset corresponds to the pore size distribution curve (B).

Scheme 2. Post graph functionalization of MSNS. Initial surface functionalization of MSNs with APTES. Amine groups of APTES react with the ester group of the bifunctional PEG. The TT1 peptides are anchored through reaction of the PEG maleimide group with the germinal cysteine end modified TT1.

Fig. 2. Radiochemical stability studies. Data bars show the percentage of remaining of ⁸⁹Zr labelled NPs incubated at 0.1 mg mL⁻¹ silica at 37 °C in simulated body fluid (SBF) and SBF with EDTA.

Fig. 3. (A) Maximum intensity coronal projections images of PET-CT image biodistribution of core labelled ⁸⁹Zr-MSNs-PEG₅₀₀₀ (upper) and ⁸⁹Zr-MSNs-PEG₅₀₀₀-TT1 (lower) after intravenous administration on xerograph B16F10 melanoma tumor bearing mice. (B) Percentage of injected dose per volume (ID cc⁻¹) of major organs at different times. (C) Results from ex vivo measurements by γ-counter represented quantification of injected dose per gram (ID g⁻¹) of major organ after intravenous administration of MSNs-PEG₅₀₀₀-¹³¹I-TT1 and labelled peptide ¹³¹I-TT1.