Water-soluble AIE photosensitizer in short-wave infrared region for albumin-enhanced and self-reporting phototheranostics.

Organic photosensitizers (PSs) play important roles in phototheranostics, and contribute to the fast development of precision medicine. However, water-soluble and highly emissive organic PSs, especially those emitting in the short-wave infrared region (SWIR), are still challenging. Also, it's difficult to prepare self-reporting PSs for visualizing the treatment via stimulated emission depletion (STED) nanoscopy. Thus, in this work, a water-soluble molecule of DTPAP-TBZ-I with aggregation-induced emission features is designed for the self-reporting photodynamic therapy (PDT) in an ultra-high resolution. In contrast to single molecule, its complex (DTPAP-TBZ-I@BSA) shows much enhanced fluorescence properties and reactive oxygen species (ROS) generation in SWIR window. Their photoluminescence quantum yield is determined to be ∼20.6 % and the enhancement of ROS generation is ∼18-fold. During the PDT, immigration of the complex from cytoplasm to nucleus is also observed via STED nanoscopy with a resolution of 66.11 nm, which allows self-report in the PDT treatment. DTPAP-TBZ-I@BSA is finally utilized for the imaging-guided PDT in vivo with a tumor inhibition rate of 84 %. This is the first work in albumin-enhanced water-soluble organic PSs in SWIR window for self-reporting phototheranostics at ultra-high resolutions, providing an ideal solution for the next generation of photosensitizers for precise medicine.

Less is More: Asymmetric D-A Type Agent to Achieve Dynamic Self-Assembled Nanoaggregates for Long-Acting Photodynamic Therapy.

To enhance the phototheranostic performance, agents with high reactive oxygen species (ROS) generation, good tumor-targeting ability, and prolonged retention are urgently needed. However, symmetric donor-acceptor (D-A) type agents usually produce spherical nanoaggregates, leading to good tumor targeting but inferior retention. Rod-like nanoaggregates are desired to extend their retention in tumors; however, this remains a challenge. In particular, agents with dynamically changeable shapes that integrate merits of different morphologies are seldomly reported. Therefore, self-assembled organic nanoaggregates with smart shape tunability are designed here using an asymmetric D-A type TIBT. The photoluminescence quantum yield in solids is up to 52.24% for TIBT. TIBT also exhibits high ROS generation in corresponding nanoaggregates (TIBT-NCs). Moreover, dynamic self-assembly in shape changing from nanospheres to nanorods occurrs in TIBT-NCs, contributing to the enhancement of ROS quantum yield from 0.55 to 0.72. In addition, dynamic self-assembly can be observed for both in vitro and in vivo, conferring TIBT-NCs with strong tumor targeting and prolonged retention. Finally, efficient photodynamic therapy to inhibit tumor growth is achieved in TIBT-NCs, with an inhibition rate of 90%. This work demonstrates that asymmetric D-A type agents can play significant roles in forming self-assembled organic nanoaggregates, thus showing great potential in long-acting cancer therapy.

One Stone, Two Birds: High-Brightness Aggregation-Induced Emission Photosensitizers for Super-Resolution Imaging and Photodynamic Therapy.

Most aggregation-induced emission (AIE) luminogens exhibit high brightness, excellent photostability, and good biocompatibility, but these AIE-active agents, which kill two birds with one stone to result in applications in both stimulated emission depletion (STED) super-resolution imaging and photodynamic therapy (PDT), have not been reported yet but are urgently needed. To meet the requirements of STED nanoscopy and PDT, D-A-π-A-D type DTPABT-HP is designed by tuning conjugated π spacers. It exhibits red-shifted emission, high PLQY of 32.04%, and impressive 1O2 generation (9.24 fold compared to RB) in nanoparticles (NPs). Then, DTPABT-HP NPs are applied in cell imaging via STED nanoscopy, especially visualizing the dynamic changes of lysosomes in the PDT process at ultrahigh resolution. After that, in vivo PDT was also conducted by DTPABT-HP NPs, resulting in significantly inhibited tumor growth, with an inhibition rate of 86%. The work here is beneficial to the design of multifunctional agents and the deep understanding of their phototheranostic mechanism in biological research.

Expression of concern: Intelligent nanoflowers: a full tumor microenvironment-responsive multimodal cancer theranostic nanoplatform.

Expression of concern for 'Intelligent nanoflowers: a full tumor microenvironment-responsive multimodal cancer theranostic nanoplatform' by Xunan Jing et al., Nanoscale, 2019, 11, 15508-15518, https://doi.org/10.1039/C9NR04768A.

Aggregation-induced emission (AIE)-active metallacycles with near-infrared emission for photodynamic therapy.

Multifunctional metallacycles with solid-state emission are highly important in cancer therapy. Here, an aggregation-induced emission (AIE)-active metallacycle of DTPABT-MC-R is developed with efficient emission in the NIR region in the solid state (PLQYs = 4.92%). DTPABT-MC-R-based nanoparticles also display excellent photo-stability, and impressive photosensitive characteristics (ROS efficiency = 10.74%), finally leading to applications in cellular imaging and photodynamic therapy (PDT).

Chitosan-based hemostatic sponges as new generation hemostatic materials for uncontrolled bleeding emergency: Modification, composition, and applications.

The choice of hemostatic technique is a curial concern for surgery and as first-aid treatment in combat. To treat uncontrolled bleeding in complex wound environments, chitosan-based hemostatic sponges have attracted significant attention in recent years because of the excellent biocompatibility, degradability, hemostasis and antibacterial properties of chitosan and their unique sponge-like morphology for high fluid absorption rate and priority aggregation of blood cells/platelets to achieve rapid hemostasis. In this review, we provide a historical perspective on the use of chitosan hemostatic sponges as the new generation of hemostatic materials for uncontrolled bleeding emergencies in complex wounds. We summarize the modification of chitosan, review the current status of preparation protocols of chitosan sponges based on various composite systems, and highlight the recent achievements on the detailed breakdown of the existing chitosan sponges to present the relationship between their composition, physical properties, and hemostatic capacity. Finally, the future opportunities and challenges of chitosan hemostatic sponges are also proposed.

Retraction: A tumor-microenvironment fully responsive nano-platform for MRI-guided photodynamic and photothermal synergistic therapy.

Retraction of 'A tumor-microenvironment fully responsive nano-platform for MRI-guided photodynamic and photothermal synergistic therapy' by Daquan Wang et al., J. Mater. Chem. B, 2020, 8, 8271-8281, https://doi.org/10.1039/D0TB01373K.

A tumor-microenvironment fully responsive nano-platform for MRI-guided photodynamic and photothermal synergistic therapy.

Multifunctional intelligent theranostics agents are promising for next-generation oncotherapy. We fabricated a tumor-microenvironment (TME)-responsive carbon nanotube (CNT)-based nanoplatform for T1 weighted magnetic resonance imaging (MRI)-guided synergistic photodynamic and photothermal therapy (PDT and PTT). CNTs convert near infrared (NIR) radiation into hyperthermia for PTT, and can effectively deliver their cargo into cells due to their unique 1D nanostructure. The CNT@MnO2-PEG@Ce6 nanomedicine was internalized into tumor cells, and rapidly released the photosensitizer (Ce6) in response to the low pH and high glutathione (GSH) levels characteristic of the TME. The degradation of the MnO2 layer under the same conditions released Mn2+ for T1-MRI. Furthermore, catalytic decomposition of the excess H2O2 into oxygen by MnO2 enhanced the efficacy of PDT, relieved hypoxia, and increased consumption of superfluous GSH to mitigate the effects of excessive reactive oxygen species (ROS) generation during PDT. MRI-guided PDT and PTT synergistically inhibited tumor cell growth in vitro, and ablated tumors in vivo. The side effects were negligible due to specific tumor cell targeting via surface modification with folic-PEG, and enhanced permeability and retention. Taken together, CNT@MnO2-PEG is a fully TME-responsive theranostics nanoplatform for targeted tumor ablation and real-time disease tracking.

Tuning molecular aggregation to achieve highly bright AIE dots for NIR-II fluorescence imaging and NIR-I photoacoustic imaging.

Currently, bright aggregation-induced emission luminogens (AIEgens) with high photoluminescence quantum yields (PLQYs) in the NIR-II region are still limited, and thus an efficient strategy to enhance NIR-II fluorescence performance through tuning molecular aggregation is proposed here. The synthesized donor-acceptor tailored AIEgen (DTPA-TBZ) not only exhibits an excellent absorptivity in the NIR-I region, but also good fluorescence signals in the NIR-II region with an emission extending to 1200 nm. Benefiting from such improved intramolecular restriction and aggregation, a significant absolute PLQY value of 8.98% was obtained in solid DTPA-TBZ. Encouragingly, the resulting AIE dots also exhibit a high relative PLQY of up to 11.1% with IR 26 as the reference (PLQY = 0.5%). Finally, the AIE dots were applied in high performance NIR-II fluorescence imaging and NIR-I photoacoustic (PA) imaging: visualization of abdominal vessels, hind limb vasculature, and cerebral vessels with high signal to background ratios was performed via NIR-II imaging; Moreover, PA imaging has also been performed to clearly observe tumors in vivo. These results demonstrate that by finely tuning molecular aggregation in DTPA-TBZ, a good NIR-I absorptivity and a highly emissive fluorescence in the NIR-II region can be achieved simultaneously, finally resulting in a promising dual-modal imaging platform for real-world applications to achieve precise cancer diagnostics.

Intelligent nanoflowers: a full tumor microenvironment-responsive multimodal cancer theranostic nanoplatform.

Although the collaborative therapy of chemotherapy (CT) and photodynamic therapy (PDT) is much more efficient for tumor treatment than monotherapies, premature leakage of drugs from nanocarriers and hypoxia in the tumor microenvironment (TME) result in systemic toxicity and suboptimal therapy efficiency. To overcome these limitations, we developed an intelligent nanoflower composite (termed FHCPC@MnO2) by coating functionalized polyphosphazene on superparamagnetic Fe3O4 nanoclusters and then growing MnO2 nanosheets as an outer shell. The FHCPC@MnO2 nanoflowers with multistage H2O2/pH/GSH-responsive properties could fully exploit TME characteristics, including supernormal glutathione (GSH) levels, low pH and high H2O2, to realize the specific release of drugs in tumors and maximum synergetic therapeutic effects. The MnO2 nanosheets can elevate O2 concentration by catalytic decomposition of H2O2 and can be simultaneously reduced to Mn2+ by overexpressed GSH in the acidic TME. Meanwhile, the inner polyphosphazene containing (bis-(4-hydroxyphenyl)-disulfide) is GSH- and pH-sensitively biodegradable to release the anticancer drug curcumin (CUR) and photosensitizer chlorin e6 (Ce6) in the TME. Therefore, the "triple-responsive" and synergetic strategy simultaneously endows the nanoflowers with specific drug release, relieving hypoxia and the antioxidant capability of the tumor and achieving significant optimization of CT and PDT. In addition, the resulting Mn2+ ions and Fe3O4 core enable in vivo T1/T2 magnetic resonance imaging (MRI), while the released Ce6 can simultaneously provide a fluorescence imaging (FL) function. Unsurprisingly, the intelligent nanoflowers exhibited remarkable multimodal theranostic performance both in vitro and in vivo, suggesting their great potential for precision medicine.