pH-Responsive NIR-II phototheranostic agents for in situ tumor vascular monitoring and combined anti-vascular/photothermal therapy.

Developing nanoplatforms integrating superior fluorescence imaging ability in second near-infrared (NIR-II) window and tumor microenvironment responsive multi-modal therapy holds great potential for real-time feedback of therapeutic efficacy and optimizing tumor inhibition. Herein, we developed a pH-sensitive pyrrolopyrrole aza-BODIPY-based amphiphilic molecule (PTG), which has a balanced NIR-II fluorescence brightness and photothermal effect. PTG is further co-assembled with a vascular disrupting agent (known as DMXAA) to prepare PTDG nanoparticles for combined anti-vascular/photothermal therapy and real-time monitoring of the tumor vascular disruption. Each PTG molecule has an active PT-3 core which is linked to two PEG chains via pH-sensitive ester bonds. The cleavage of ester bonds in the acidic tumor environment would tricker releases of DMXAA for anti-vascular therapy and further assemble PT-3 cores into micrometer particles for long term monitoring of the tumor progression. Furthermore, benefiting from the high brightness in the NIR-II region (119.61 M-1 cm-1) and long blood circulation time (t1/2 = 235.6 min) of PTDG nanoparticles, the tumor vascular disrupting process can be in situ visualized in real time during treatment. Overall, this study demonstrates a self-assembly strategy to build a pH-responsive NIR-II nanoplatform for real-time monitoring of tumor vascular disruption, long-term tracking tumor progression and combined anti-vascular/photothermal therapy.

Pyrrolopyrrole aza-BODIPY-based NIR-II fluorophores for in vivo dynamic vascular dysfunction visualization of vascular-targeted photodynamic therapy.

Real-time monitoring vascular responses is crucial for evaluating the therapeutic effects of vascular-targeted photodynamic therapy (V-PDT). Herein, we developed a highly-stable and bright aggregation induced emission (AIE) fluorophore (PTPE3 NP) for dynamic fluorescence (FL) imaging of vascular dysfunction beyond 1300 nm window during V-PDT. The superior brightness (ϵmaxΦf>1000 nm ≈ 180.05 M-1 cm-1) and high resolution of PTPE3 NP affords not only high-clarity images of whole-body and local vasculature (hindlimbs, mesentery, and tumor) but also high-speed video imaging for tracking blood circulation process. By virtue of the NPs' prolonged blood circulation time (t1/2 ≈ 86.5 min) and excellent photo/chemical (pH, RONS) stability, mesenteric and tumor vascular dysfunction (thrombosis formation, vessel occlusion, and hemorrhage) can be successfully visualized during V-PDT by FL imaging for the first time. Furthermore, the reduction of blood flow velocity (BFV) can be monitored in real time for precisely evaluating efficacy of V-PDT. These provide a powerful approach for assessing vascular responses during V-PDT and promote the development of advanced fluorophores for biological imaging.

Heterostrain-enabled ultrahigh electrostrain in lead-free piezoelectric.

Piezoelectric materials provide high strain and large driving forces in actuators and can transform electrical energy into mechanical energy. Although they were discovered over 100 years ago, scientists are still searching for alternative lead-free piezoelectrics to reduce their environmental impact. Developing high-strain piezoelectric materials has been a long-term challenge, particularly challenging for the design of high-strain polycrystalline piezoelectrics containing no toxic lead element. In this work, we report one strategy to enhance the electrostrain via designing "heterostrain" through atomic-scale defect engineering and mesoscale domain engineering. We achieve an ultrahigh electrostrain of 2.3% at high temperature (220 °C) in lead-free polycrystalline ceramics, higher than all state-of-the-art piezoelectric materials, including lead-free and lead-based ceramics and single crystals. We demonstrate practical solutions for achieving high electrostrain in low-cost environmentally piezoelectric for various applications.

Amphiphilic Diketopyrrolopyrrole Derivatives for Efficient Near-Infrared Fluorescence Imaging and Photothermal Therapy.

The design and synthesis of single-molecule amphiphilic and multifunctional phototherapeutic agents are important to cancer diagnosis and therapy. In this work, we developed three amphiphilic diketopyrrolopyrrole derivatives (TPADPP, DTPADPP, and TPADDPP) with different donor-acceptor structures and poly(ethylene glycol) side chains. The corresponding nanoparticles (NPs) were obtained via a self-assembly from three amphiphilic DPP derivatives and used as smart phototherapeutic agents for tumor diagnosis and treatment. The three amphiphilic DPP NPs exhibited near-infrared (NIR) emissions and good biocompatibility. Thus, they could be used as fluorescence (FL) imaging agents for guided therapy. DTPADPP NPs and TPADDPP NPs also displayed excellent photothermal performance and high accumulation in the tumor. Owing to these beneficial features, the DTPADPP NPs and TPADDPP NPs synthesized herein are suitable for NIR FL imaging and effective photothermal therapy against the tumor in vivo.