Upconversion nanoparticles (UCNPs) are prospective platforms for bioimaging and phototherapy, but a critical bottleneck is the limited brightness due to the faint absorptivity of lanthanide ions and the low quantum yield. To circumvent this problem, we herein propose our strategy to reconstruct the energy cascade of UCNPs using semiconductor quantum dots (QDs) as light sensitizer of Nd3+/Yb3+ codoped UCNPs. Ag2Se QDs with strong absorption at 808 nm acted as efficient antenna and transferred their energy to Yb3+ via a resonance energy transfer process, significantly enhancing the luminescence of UCNPs. This nanocomposite was then combined with Rose Bengal and applied for photodynamic therapy. Both in vitro and in vivo studies revealed the introduction of QDs improved the therapeutic performance remarkably. Our study suggests Ag2Se QDs with excellent photophysical properties can be promising agents to overcome the shortcomings of UCNPs and further strengthen their applications.

Intraoperative visualization of the full extent of brain tumor by luminescence imaging helps to improve the degree and accuracy of brain tumor resection, thereby prolonging the survival of patients. However, the limited imaging depth and spatial resolution and the poor blood‐brain barrier (BBB) permeability of most currently available luminescent probes restrict the imaging performance and surgical resection efficiency of brain tumor. Here, a brain tumor cell membrane‐coated lanthanide‐doped nanoparticles (CC‐LnNPs) in the near‐infrared‐IIb window (NIR‐IIb, 1500–1700 nm) is designed for brain tumor imaging and surgical navigation. The coating of brain tumor cell membrane endows CC‐LnNPs with immune escape, BBB crossing, and homotypic targeting abilities, which are inherited from the source brain tumor cells. In addition, compared with clinically approved imaging agent indocyanine green, CC‐LnNPs present higher temporal and spatial resolution, higher stability, and lower background signals, enabling clear visualization of the brain tumor boundary. With the guidance of NIR‐IIb fluorescence, the glioma tissue (size < 3 mm, depth > 3 mm) could be clearly visualized and completely removed as a proof of concept. This study offers new insight for the future design of nanoprobe to image brain tumor and to achieve precise diagnosis and surgical navigation of brain tumor.

A two-photon fluorescent probe FNTR for nitroreductase was synthesized by using 9,9-dimethyl-2-acetyl-fluoren-7-methylamino (1) as a two-photon fluorophore and a p-nitrobenzyl carbamate group as a recognition domain for nitroreductase (NTR). The probe and the fluorophore were tested under one- and two-photon modes respectively. After reacting with nitroreductase, FNTR had a 130-fold fluorescence enhancement at 563 nm in 10 min and the maximal two-photon action cross-section value was detected as 66 GM at 750 nm. The probe showed a high sensitivity with a detection limit as low as 23.67 ng ml, high selectivity, low cytotoxicity and good photostability. In the presence of reduced nicotinamide adenine dinucleotide (NADH), endogenous NTR was detected in living cells, tissues and zebrafish. Cobalt chloride was used to induce chemical hypoxia to produce NTR, which generated enhanced fluorescence in cells and tumor tissues. Finally, two-photon fluorescence imaging of NTR was achieved in zebrafish at a penetration depth of up to 200 μm.

Real-time and in situ visualization of cerebrovascular dysfunction is significant for studying brain injury, which however, is restricted by the complex brain structure and limited imaging strategies. Luminescence imaging in NIR-IIb region (1500−1700 nm) is a promising tool owing to its merits including deep penetration, high resolution, and fast data acquisition. Unfortunately, a luminescent material in this region with sufficient brightness and biocompatibility is scarce. Herein, Ag 2 Se quantum dot-sensitized lanthanide-doped nanocrystals (QDs-LnNCs) with emission beyond 1500 nm were fabricated to image the cerebrovascular structure and hemodynamics in ischemic stroke and traumatic brain injury. The sensitization by QDs provided an over 100-fold enhanced brightness of LnNCs and a remarkable penetration depth of 11 mm. Dynamic information of blood perfusion and flow rates were acquired and the damage of the blood−brain barrier in the two injury models was investigated. Our results proved QDs-LnNCs as a kind of competent nanomaterial for noninvasive brain imaging.

Hydroxyl radical (·OH), as the most deleterious reactive oxygen species, is believed to be the etiological agent for many diseases and aging. An altered ·OH level has been confirmed in certain types of superoxide dismutase (SOD) mutation, but the regulation of ·OH by SOD in situ is still controversial or unclear because of the lack of effective tools to detect ·OH in the biological environment. Herein we report the first two-photon excitable molecular probe (P2) for ·OH, which is able to track the subtle fluctuation of ·OH level both in vitro and in vivo with high sensitivity and specificity. The probe was successfully applied to visualize ·OH variations in a variety of SOD1-involved biological processes, confirming that the inhibited enzymatic activity and down-regulated expression of SOD1 both lead to elevated intracellular ·OH level. This is the first report to visually reveal the relationship between SOD1 and ·OH level with a molecular tool.