Description
In this work, we propose a three-dimensional (3D) nonlinear optical imaging scheme for the spectroscopic characterization of drug delivery system (DDS) nanoparticles based on a nonlinear confocal microscope. In recent years, numerous drug delivery system (DDS) nanoparticles, such as liposomes and micelles, have been engineered to achieve drug release by utilizing pH-responsive structural changes, including degradation, swelling, and shrinkage. However, the spatiotemporally complex nature of these dynamic processes poses significant challenges for conventional analytical approaches. Accordingly, there is a pressing need for advanced methodologies that enable real-time three-dimensional spectroscopic characterization. Conventional optical microscopy is fundamentally limited by diffraction, resulting in insufficient spatial resolution for nanoparticles with dimensions below λ/2. Consequently, fluorescence labeling is often employed for visualization; however, the use of exogenous probes introduces potential cytotoxicity and perturbs the intrinsic properties of DDS nanoparticles, particularly in drug-loaded systems.
To overcome these limitations, the proposed method enables label-free, super-resolution 3D imaging of DDS nanoparticles beyond the diffraction limit. The approach leverages optically induced third-order nonlinear polarization arising from intrinsic or embedded chromophores, allowing high-fidelity structural characterization of individual nanoscale particles. Furthermore, by incorporating a vectorial polarization interferometer into the nonlinear confocal optical system, we realize a vector-resolved nonlinear spectroscopic modality. This configuration enables three-dimensional mapping of the spatial distribution and orientational characteristics of organic chromophores within single nanoparticles, as well as the resolution of ultrafine surface features.
| I am the presenting author | Yes |
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