Band Gap Engineering Improves Three-Photon Luminescence of Quantum Dots for Deep Brain Imaging

Abstract

Three-photon fluorescence microscopy (3PFM) has emerged as a promising tool in monitoring the structures and functions of the brain. Compared to the various imaging technologies, 3PFM enables a deep-penetrating depth attributed to tighter excitation confinement and suppressed photon scattering. However, the shortage of three-photon probes with a large absorption cross section (σ3) substantially limits its uses. Herein, CdSe/CdS/ZnS quantum dots (QDs) with enhanced 3PF performance were synthesized via the band gap engineering strategy. The introduction of a CdS interlayer with optimized thickness between the emitting CdSe core and the ZnS shell significantly enhanced the 3P absorption cross section of QDs, which originated from the intrinsic piezoelectric polarization effect and the change of the core/shell structure from type-I to quasi-type-II. In addition, the outer ZnS layer compensated the poor electronic passivation of CdS, providing a high level of passivation for the improvement of quantum yield as well as the 3P action cross section of QDs. Under the excitation of a 1600 nm femtosecond laser, PEGylated CdSe/CdS/ZnS QDs were used for in vivo 3PFM imaging of cerebral vessels with high resolution. A tiny capillary with a diameter of 0.8 μm could be resolved at the imaging depth of 1550 μm in a mouse brain with an opened skull. A penetration depth of 850 μm beneath the skull was also achieved using a mouse model with an intact skull.

Bioorthogonal NIR-IIb Quantum Dots for Imaging-Guided Photothermal Therapy

“…The metabolic labeling of Az-NPs was investigated by cellular imaging using DBCO-CdSe/ZnS QDs emitting at 632 nm (Figure S2). 40 Before the cell labeling experiment, we first detected the cytotoxicity of Az-NPs and DBCO-CdSe/ZnS QDs to mouse fibroblasts (L929) and mouse breast cancer cells (4T1). The cell viabilities remained above 90% after incubation with Az-NPs or DBCO-CdSe/ZnS QDs, indicating their low toxicity to living cells (Figure S3).…”

Improving Three-Photon Fluorescence of Near-Infrared Quantum Dots for Deep Brain Imaging by Suppressing Biexciton Decay

“…The nonlinear optical properties of these QDs were investigated on a lab-developed measurement system equipped with a 1600 nm fs laser as the excitation source . The three-photon fluorescence spectrum of CdTe/CdSe/ZnS QDs almost coincided with the single-photon fluorescence spectrum (Figure a).…”

“…Owing to the rigorous requirement of the 3P process, only limited materials have been developed for 3PFM, including endogenous fluorescent proteins, organic molecules, aggregation-induced emission (AIE) luminogens, and carbon nanomaterials. − Moreover, the emission wavelengths of most 3P materials concentrate in the visible region (400–700 nm). − Considering the effective attenuation length of light with longer wavelength, the exploration of 3P materials emitting in the NIR region would be a promising direction of 3PFM. Attributed to the quantum confinement effect, quantum dots (QDs) exhibit favorable features for 3PFM, including broad excitation range, emission tunability, and enhanced optical nonlinearity. ,− It is possible to prepare QD-based three-photon fluorescent (3PF) probes emitting in the NIR region, which could be excited by an NIR-II light source. In addition, QDs can tolerate high laser power because of their superior photostability, making them an ideal choice for 3PFM.…”