Fluorination Enhances NIR-II Fluorescence of Polymer Dots for Quantitative Brain Tumor Imaging.

Here, we describe a fluorination strategy for semiconducting polymers for the development of highly bright second near-infrared region (NIR-II) probes. Tetrafluorination yielded a fluorescence QY of 3.2 % for the polymer dots (Pdots), over a 3-fold enhancement compared to non-fluorinated counterparts. The fluorescence enhancement was attributable to a nanoscale fluorous effect in the Pdots that maintained the molecular planarity and minimized the structure distortion between the excited state and ground state, thus reducing the nonradiative relaxations. By performing through-skull and through-scalp imaging of the brain vasculature of live mice, we quantitatively analyzed the vascular morphology of transgenic brain tumors in terms of the vessel lengths, vessel branches, and vessel symmetry, which showed statistically significant differences from the wild type animals. The bright NIR-II Pdots obtained through fluorination chemistry provide insightful information for precise diagnosis of the malignancy of the brain tumor.

Near-Infrared II Semiconducting Polymer Dots: Chain Packing Modulation and High-Contrast Vascular Imaging in Deep Tissues.

Fluorescence imaging in the second near-infrared (NIR-II) window has attracted considerable interest in investigations of vascular structure and angiogenesis, providing valuable information for the precise diagnosis of early stage diseases. However, it remains challenging to image small blood vessels in deep tissues because of the strong photon scattering and low fluorescence brightness of the fluorophores. Here, we describe our combined efforts in both fluorescent probe design and image algorithm development for high-contrast vascular imaging in deep turbid tissues such as mouse and rat brains with intact skull. First, we use a polymer blending strategy to modulate the chain packing behavior of the large, rigid, NIR-II semiconducting polymers to produce compact and bright polymer dots (Pdots), a prerequisite for in vivo fluorescence imaging of small blood vessels. We further developed a robust Hessian matrix method to enhance the image contrast of vascular structures, particularly the small and weakly fluorescent vessels. The enhanced vascular images obtained in whole-body mouse imaging exhibit more than an order of magnitude improvement in the signal-to-background ratio (SBR) as compared to the original images. Taking advantage of the bright Pdots and Hessian matrix method, we finally performed through-skull NIR-II fluorescence imaging and obtained a high-contrast cerebral vasculature in both mouse and rat models bearing brain tumors. This study in Pdot probe development and imaging algorithm enhancement provides a promising approach for NIR-II fluorescence vascular imaging of deep turbid tissues.

Light-Controlled Precise Delivery of NIR-Responsive Semiconducting Polymer Nanoparticles with Promoted Vascular Permeability.

The endothelial barrier plays an essential role in health and disease by protecting organs from toxins while allowing nutrients to access the circulation. However, it is the major obstacle that limits the delivery of therapeutic drugs to the diseased tissue. Here, it is reported for the first time that near-infrared (NIR) laser pulses can transiently promote the delivery of semiconducting polymer nanoparticles passing the vascular barrier via photoacoustic-effect-induced accumulation, only by the aid of pulse laser irradiation. This strategy enables selective and substantial accumulation of the NIR-absorbing nanoparticles inside specific tissues, implying the discovery of an unprecedented approach for light-controlled nanoparticle delivery. Especially, the nanoparticle delivery in solid tumors by 10-min laser scanning is approximately six times higher than that of the enhanced permeability and retention (EPR) effect in 24 h under current experimental conditions. Further results confirm that this strategy facilitates substantial accumulation of nanoparticles in the mouse brain with intact skull. This approach thus opens a new door for tissue-specific delivery of nanomaterials with an unprecedented level of efficiency and precision.