Dual-targeted organic nanoparticles efficiently target the margin of glioblastoma and successfully suppress the tumour growth through photothermal therapy.

As conjugated polymer nanoparticles (CPNs) have attracted growing interest as photoacoustic (PA) imaging contrast agents, revelation of the relationship between the molecular structure of conjugated polymers and PA property is highly in demand. Here, three donor-acceptor-structured conjugated polymer analogs are designed, where only a single heteroatom of acceptor units changes from oxygen to sulfur to selenium, allowing for systematic investigation of the molecular structure-PA property relationship. The absorption and PA spectra of these CPNs can be facilely tuned by changing the heteroatoms of the acceptor units. Moreover, the absorption coefficient, and in turn the PA signal intensity, decreases when the heteroatom changes from oxygen to sulfur to selenium. As these CPNs exhibit weak fluorescence and similar photothermal conversion efficiency (≈70%), their PA intensities are approximately proportional to their absorption coefficients. The in vivo brain vasculature imaging in this study also demonstrates this trend. This study provides a simple but efficient strategy to manipulate the PA properties of CPNs through changing the heteroatom at key positions.

Stem-cell based therapy is an emerging therapeutic approach for ischemic stroke treatment. Bone marrow stromal cells (BMSCs) are in common use as a cell source for stem cell therapy and show promising therapeutic outcomes for stroke treatment. One challenge is to develop a reliable tracking strategy to monitor the fate of BMSCs and assess their therapeutic effects in order to improve the success rate of such treatment. Herein, TPEEP, a fluorogen with aggregation-induced emission characteristics and near-infrared emission are designed and synthesized and further fabricated into organic nanoparticles (NPs). The obtained NPs show high fluorescence quantum yield, low cytotoxicity with good physical and photostability, which display excellent tracking performance of BMSCs in vitro and in vivo. Using a rat photothrombotic ischemia model as an example, the NP-labeled BMSCs are able to migrate to the stroke lesion site to yield bright red fluorescence. Immunofluorescence staining shows that the NP labeling does not affect the normal function of BMSCs, proving their good biocompatibility in vivo. These merits make TPEEP NP a potential cell tracker to evaluate the fate of BMSCs in cell therapy.

Stroke is a common disease and a severe threat to human health, especially with its increasing prevalence in the rapidly growing aged population. It is the second-most frequent cause of death and long-term disability. [1,2] Ischemic stroke, caused by an obstruction of cerebrovascular blood flow due to a blood clot (thrombus), accounts for two-thirds of stroke occurrences. [3,4] Currently, the only FDA-approved treatment for ischemic stroke is thrombolysis using recombinant tissue plasminogen activator (tPA), which dissolves blood clots, recanalizes the occluded vessel, and restores blood flow to the ischemic tissue. [5] However, it is effective only when administered within a time window of 4.5 h of stroke occurrence. [6,7] In addition, the time to recanalization has also been proven to be a key indicator of clinical outcomes. A crucial element to timely recanalization and reduced door-to-needle time is patient triaging. Clinical imaging techniques hold the key to not only establishing patient selection for stroke therapy, but also managing treatment and post-treatment monitoring of reperfusion. The most commonly used clinical imaging techniques including computed tomography (CT) and magnetic resonance imaging (MRI), are limited to a first-line scan to establish the status of stroke to be either ischemic or hemorrhagic in nature. [8] Once ascertained to be an ischemic stroke, administration of thrombolytics requires ascertainment of an occlusion and real-time monitoring of recanalization which is currently carried out using transcranial doppler ultrasound (TCD). However, TCD is a blind technique that is highly operator skill dependent and provides no accurate and evident information on the magnitude and specifics of successful thrombolysis. On the other hand, the tPA treatment does not always lead to optimal treatment outcome due to its short half-life (<5 min), [9] and it has a propensity to cause hemorrhagic transformation in the surrounding healthy tissue. [10] Thus, it is highly desirable to develop a new platform that can realize fast image-aided recanalization monitoring and also enhance the therapeutic effect of tPA.Photoacoustic (PA) imaging is an emerging imaging technique, which is based on the detection of acoustic waves generated by PA contrast agents. These agents are capable of absorbing light and converting it into kinetic energy or localized heating through nonradiative decay pathways. [11,12] As compared with

Ischemic stroke is one of the leading causes of death and disability in the world. Thrombolytic therapy using recombinant tissue plasminogen activator (rtPA), the only FDA-approved drug for acute ischemia, is limited by a narrow therapeutic time window and risk of hemorrhage. There is a serious need for a neuroprotective therapy which is clinically viable. We earlier demonstrated that peripheral sensory stimulation (PSS) is a potential therapeutic intervention for hyperacute ischemia resulting in recovery of neurovascular functions when administered immediately following ischemia onset in a rat model. Here, we investigated the potential neuroprotective effect of PSS during the hyperacute phase of stroke in a rat photothrombotic ischemia (PTI) model. We employed electrocorticography (ECoG) to image cortical neural activity responses pre-and post-ischemia. Results showed that the neural activity including somatosensory evoked potentials (SSEPs) and alpha-to-delta ratio (ADR) were restored following administration of PSS. Further, immunohistochemistry and TTC staining also indicated the neuroprotective effect of PSS intervention, protecting more neurons and reduced infarct. Overall, the study demonstrated that PSS administered immediately following ischemia induction in a rat PTI model can significantly promote neuroprotection via inhibition of peri-infarct expansion and enhanced cortical neural activity functions, suggesting effective recovery. Future work utilizing multimodal imaging to probe changes in neurovascular functions, will explore application of PSS as an adjuvant intervention for improving rtPA thrombolysis therapy.

Long‐term tracking of bone marrow stromal cells in a rat photothrombotic ischemia model is achieved by organic nanoparticles with aggregation‐induced emission. On page 6576, L.‐D. Liao, B. Liu, and co‐workers demonstrate the design and synthesis of the nanoparticles to realize low phototoxicity and high stability. These nanoparticles show promising potential for monitoring the transplanted stem cells in cell therapy.