Theranostic systems combining fluorescence imaging in the second near-infrared window (NIR-II, 1000–1700 nm) and photothermal therapy (PTT) under safe laser fluence have great potential in preclinical research and clinical practice, but the development of such systems with sufficient effective NIR-II brightness and excellent photothermal properties is still challenging. Here we report a theranostic system based on semiconducting polymer nanoparticles (L1057 NPs) for NIR-II fluorescence imaging and PTT under a 980 nm laser irradiation, with low (25 mW/cm2) and high (720 mW/cm2) laser fluence, respectively. Taking into consideration multiple parameters including the extinction coefficient, the quantum yield, and the portion of emission in the NIR-II region, L1057 NPs have much higher effective NIR-II brightness than most reported organic NIR-II fluorophores. The high brightness, together with good stability and excellent biocompatibility, allows for real-time visualization of the whole body and brain vessels and the detection of cerebral ischemic stroke and tumors with high clarity. The excellent photothermal properties and high maximal permissible exposure limit at 980 nm allow L1057 NPs for PTT of tumors under safe laser fluence. This study demonstrates that L1057 NPs behave as an excellent theranostic system for NIR-II imaging and PTT under safe laser fluence and have great potential for a wide range of biomedical applications.

Second near-infrared (NIR-II, 1000−1700 nm) fluorescence bioimaging has attracted tremendous scientific interest and already been used in many biomedical studies. However, reports on organic NIR-II fluorescent probes for in vivo photoinduced imaging and simultaneous therapy, as well as the longterm tracing of specific biological objects, are still very rare. Herein we designed a single-molecular and NIR-II-emissive theranostic system by encapsulating a kind of aggregation-induced emission luminogen (AIEgen, named BPN-BBTD) with amphiphilic polymer. The ultra-stable BPN-BBTD nanoparticles were employed for the NIR-II fluorescence imaging and photothermal therapy of bladder tumors in vivo. The 785 nm excitation triggered photothermal therapy could completely eradicate the subcutaneous tumor and inhibit the growth of orthotopic tumors. Furthermore, BPN-BBTD nanoparticles were capable of monitoring subcutaneous and orthotopic tumors for a long time (32 days). Single-molecular and NIR-II-emitted aggregation-induced emission nanoparticles hold potential for the diagnosis, precise treatment, and metastasis monitoring of tumors in the future.

Imaging the brain with high integrity is of great importance to neuroscience and related applications. X-ray computed tomography (CT) and magnetic resonance imaging (MRI) are two clinically used modalities for deep-penetration brain imaging. However, their spatial resolution is quite limited. Two-photon fluorescence microscopic (2PFM) imaging with its femtosecond (fs) excitation wavelength in the traditional near-infrared (NIR) region (700-1000 nm) is able to realize deep-tissue and high-resolution brain imaging. However, it requires craniotomy and cranial window or skull-thinning techniques due to photon scattering of the excitation light. Herein, based on a type of aggregation-induced emission luminogen (AIEgen) DCDPP-2TPA with a large three-photon absorption (3PA) cross section at 1550 nm and deep-red emission, we realized through-skull three-photon fluorescence microscopic (3PFM) imaging of mouse cerebral vasculature without craniotomy and skull-thinning. Reduced photon scattering of a 1550 nm fs excitation laser allowed it to effectively penetrate the skull and tightly focus onto DCDPP-2TPA nanoparticles (NPs) in the cerebral vasculature, generating bright three-photon fluorescence (3PF) signals. In vivo 3PF images of the cerebral vasculature at various vertical depths were obtained, and a vivid 3D reconstruction of the vascular architecture beneath the skull was built. As deep as 300 μm beneath the skull, small blood vessels of 2.4 μm could still be recognized.

Fluorescence bioimaging in the second near‐infrared spectral region (NIR‐II, 1000–1700 nm) can provide advantages of high spatial resolution and large penetration depth, due to low light scattering. However, NIR‐II fluorophores simultaneously possessing high brightness, good stability, and biocompatibility are very rare. Hydrophobic NIR‐II emissive PbS@CdS quantum dots (QDs) are surface‐functionalized, via a silica and amphiphilic polymer (Pluronic F‐127) dual‐layer coating method. The as‐synthesized PbS@CdS@SiO2@F‐127 nanoparticles (NPs) are aqueously dispersible and possess a quantum yield of ≈5.79%, which is much larger than those of most existing NIR‐II fluorophores. Thanks to the dual‐layer protection, PbS@CdS@SiO2@F‐127 NPs show excellent chemical stability in a wide range of pH values. The biocompatibility of PbS@CdS@SiO2@F‐127 NPs is studied, and the results show that the toxicity of the NPs in vivo could be minimal. PbS@CdS@SiO2@F‐127 NPs are then utilized for in vivo and real‐time NIR‐II fluorescence microscopic imaging of mouse brain. The architecture of blood vessels is visualized and the imaging depth reaches 950 µm. Furthermore, in vivo NIR‐II fluorescence imaging of gastrointestinal tract is achieved, by perfusing PbS@CdS@SiO2@F‐127 NPs into mice at a rather low dosage. This work illustrates the potential of ultrastable, biocompatible, and bright NIR‐II QDs in biomedical and clinical applications, which require deep tissue imaging.

Visualization of the brain in its native environment is important for understanding common brain diseases. Herein, bright luminogens with remarkable aggregation‐induced emission (AIE) characteristics and high quantum yields of up to 42.6% in the solid state are synthesized through facile reaction routes. The synthesized molecule, namely BTF, shows ultrabright far‐red/near‐infrared emission and can be fabricated into AIE dots by a simple nanoprecipitation procedure. Due to their high brightness, large Stokes shift, good biocompatibility, satisfactory photostability, and large three‐photon absorption cross section, the AIE dots can be utilized as efficient fluorescent nanoprobes for in vivo brain vascular imaging through the intact skull by a three‐photon fluorescence microscopy imaging technique. This is the first example of using AIE dots for the visualization of the cerebral stroke process through the intact skull of a mouse with high penetration depth and good image contrast. Such good results are anticipated to open up a new venue in the development of efficient emitters with strong nonlinear optical effects for noninvasive bioimaging of living brain.

Aggregation-induced emission nanoparticles, TPE-red–PSMA, were prepared and used as photosensitizers for two-photon excited photodynamic therapy under 1040 nm fs laser excitation.

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Indocyanine green (ICG) is a favorable fluorescence nanoprobe for its strong NIR-I fluorescence emission and good photothermal capabilities. However, the stability and tumor targeting ability of ICG is poor, which limits its further applications. To further improve the photothermal and therapeutic efficiency of ICG, bovine serum albumin (BSA) was utilized to encapsulate the ICG and the chemotherapeutic drug doxorubicin (DOX) was loaded to form the BSA@ICG-DOX theranostic nanoplatform. Methods: In this study, ICG-loaded BSA nanoparticles (NPs) and the BSA@ICG-DOX NPs were fabricated using reprecipitation methods. Next, the tumour inhibition ability and biocompatibility of the NPs were evaluated. A subcutaneous xenografted nude mice model was established and imaging guided synergetic therapy was performed with the assistance of BSA@ICG-DOX NPs under 808 nm laser irradiation. Results: The BSA@ICG NPs exhibited strong NIR-I fluorescence emission, excellent photothermal properties, biocompatibility, and tumor targeting ability. To further improve the therapeutic efficiency, the chemotherapeutic drug doxorubicin (DOX) was loaded into the BSA@ICG NPs to form the BSA@ICG-DOX theranostic nanoplatform. The BSA@ICG-DOX NPs were spherical with an average size of ~194.7 nm. The NPs had high encapsulation efficiency (DOX: 19.96% and ICG: 60.57%), and drug loading content (DOX: 0.95% and ICG: 3.03%). Next, excellent NIR-I fluorescence and low toxicity of the BSA@ICG-DOX NPs were verified. Targeted NIR-I fluorescence images were obtained after intravenous injection of the NPs into the subcutaneous cervical tumors of the mice. Conclusion:To improve the anti-tumor efficiency of the ICG@BSA NPs, the chemotherapeutic drug DOX was loaded into the BSA@ICG NPs. The NIR excitation/emission and targeted BSA@ICG-DOX NPs enables high-performance diagnosis and chemo/photothermal therapy of subcutaneous cervical tumors, providing a promising approach for further biomedical applications.