Stabilization Mechanism of a Self-synthesized Nanobiosensor, DiR Accommodated Solid Lipid Nanoparticles

Introduction

Nanobiosenors, i.e., probes encapsulated in nanoparticles, have been widely employed in disease diagnosis and pharmacokinetic analysis. In our published work, a probe with a dialkylcarbocyanines skeleton (generally known as DiR) was incorporated into solid lipid nanoparticles (SLNs) to produce DiR-SLN, which was intended for biological fate tracking after pulmonary delivery. As shown by the previous results, the self-synthesized DiR-SLN possessed great chemical and physical stability during storage. Of note is that the stabilization mechanism of such a system remained unclear. Based on a preliminary study and literature survey, we hypothesized that the strong interaction between DiR molecules and SLN carrier materials guaranteed great stability. In order to validate this hypothesis, we examined the interaction between DiR and the main components of SLN, viz. cetyl palmitate (CP) and Tween 80 (T80) by the isothermal titration calorimetry (ITC) technique.

Methods

ITC was a technology commonly used in biochemistry to unravel the interaction pattern between various molecules. In the present study, titrations of DiR towards CP and DiR towards T80 were performed, in a cosolvent of 98% acetone–water (v/v). The tests were conducted in triplicates.

Results

It was shown that both DiR-CP and DiR-T80 titrations exhibited negative peaks (peak value -2 and -4 μcal/s, respectively), suggesting exothermal interaction modes. After integration processing, the change in enthalpy (ΔH) was calculated to be approximately -5 and -20 kcal/mol for DiR-CP and DiR-T80, respectively. Considering the exothermal nature and the ΔH values, it was inferred that weak (in DiR-CP) and moderate (in DiR-T80) hydrogen bonds were generated.

Conclusions

The hydrogen bonds between cargo and carrier might be a critical contributor to system stability. Our study provided a potential approach to analyze the stabilization mechanism of nanobiosenors, which could pave the way for the future studies.