ICG/Lecithin: A promising theranostic agent for simultaneous therapy and diagnosis of MRI and PAI

A chronic liver disease usually results in iron accumulation, and an excess of iron will further aggravate liver injury, forming a vicious circle. Likewise, it also plays a significant role in other organs when it comes to iron metabolism. A long time passes between the time it takes to break through to MRIbased iron diagnosis and its ability to distinguish the types of iron accumulation accurately and quickly.This work highlighted a new type of iron accumulation treatment solution integrated with diagnosis and treatment. A chelating method for ICG and Leci that can assist PAI and MRI to achieve better diagnostic and therapeutic effects. This work revealed biomaterial engineering techniques are being adapted to address clinical medical problems through cutting-edge research.

A β-sheet-targeted theranostic agent for diagnosing and preventing aggregation of pathogenic peptides in Alzheimer’s disease

Amyloid-βpeptide(Aβ)aggregates,particularly Aβoligomers,are established biomarker and toxic species in Alzheimer’s disease(AD).Early detection and disaggregation of Aβaggregates are of great importance for the treatment of AD due to the unavailability of therapy at the advanced stages of the disease.A multitalented agent,2-{2-[(1 H-benzoimidazol-2-yl)methoxy]phenyl}benzothiazole(BPB),is designed by merging twoβ-sheet targeting groups into one molecule to detect and inhibit the Aβaggregation.BPB can quantitatively measure theβ-sheet level of soluble Aβoligomers and specifically distinguish the aggregates of Aβ40 and Aβ42 by unique luminescence spectrum.Animal tests demonstrate that BPB can efficiently penetrate the blood brain barrier and precisely stain Aβplaques in the brain;more importantly,it can differentiate the blood of APP transgenic mice from that of normal ones.In addition to the diagnostic potential,BPB also suppresses the generation of ROS,protects the neurons from neurotoxicity,and disaggregates the Aβaggregates in brain homogenates of APP transgenic mice induced by metal ions or self-assembly.In view of its detective ability toward Aβoligomers and inhibition to Aβ-related neurotoxicity,BPB may be developed into a sensitive probe for screening blood samples in the early diagnosis of AD as well as an effective inhibitor for diminishing Aβaggregates in the treatment of the disease.

Tiny 2D silicon quantum sheets:a brain photonic nanoagent for orthotopic glioma theranostics

We report that atomically thin two-dimensional silicon quantum sheets(2D Si QSs),prepared by a scalable approach coupling chemical delithiation and cryo-assisted exfoliation,can serve as a highperformance brain photonic nanoagent for orthotopic glioma theranostics.With the lateral size of approximately 14.0 nm and thickness of about 1.6 nm,tiny Si QSs possess high mass extinction coefficient of 27.5 Lg^(-1)cm^(-1)and photothermal conversion efficiency of 47.2%at 808 nm,respectively,concurrently contributing to the best photothermal performance among the reported 2 D mono-elemental materials(Xenes).More importantly,Si QSs with low toxicity maintain the trade-off between stability and degradability,paving the way for practical clinical translation in consideration of both storage and action of nanoagents.In vitro Transwell filter experiment reveals that Si QSs could effectively go across the b End.3 cells monolayer.Upon the intravenous injection of Si QSs,orthotopic brain tumors are effectively inhibited under the precise guidance of photoacoustic imaging,and the survival lifetime of brain tumor-bearing mice is increased by two fold.Atomically thin Si QSs with strong light-harvesting capability are expected to provide an effective and robust 2D photonic nanoplatform for the management of brain diseases.

Construction of smart inorganic nanoparticle-based ultrasound contrast agents and their biomedical applications

Ultrasound(US) imaging in combination with US contrast agents(UCAs) is a powerful tool in the modern biomedical field because of its high spatial resolution, easy access to patients and minimum invasiveness.The microbubble-based UCAs have been widely used in clinical diagnosis; however, they are only limited to the blood pool imaging and not applicable to the tissue-penetrated imaging due to their large particle size and structural instability. Inorganic nanoparticles(NPs), such as silica,gold and Fe x O y, featured with both satisfactory echogenic properties and structural stability have the potential to be used as a new generation of UCAs. In this review, we present the most recent progresses in the tailored construction of inorganic UCAs and their biomedical applications in the US imaging-involved fields. Firstly, the typical inorganic NPs with different structures including solid, hollow and multiple-layer forms will be comprehensively introduced in terms of their structure design,physicochemical property, US imaging mechanism and diverse applications; secondly, the recent progress in exploring the gas-generating inorganic NP system for US imaging purpose will be reviewed, and these intelligent UCAs are multifunctional for simultaneous US imaging and disease therapy; thirdly, several nanocomposite platforms newly constructed by combining inorganic UCAs with other functional components will be presented anddiscussed. These multifunctional NPs are capable of further enhancing the imaging resolution by providing more comprehensive anatomical information simultaneously.Last but not the least, the design criteria for developing promising UCAs to satisfy both clinical demands and optimized US imaging capability will be discussed and summarized in this review.

Polyethylene glycol-modified cobalt sulfide nanosheets for high-performance photothermal conversion and photoacoustic/magnetic resonance imaging

Theranostic nanoagents that integrate the diagnoses and therapies within a single nanomaterial are compelling in their use for highly precise and efficient antitumor treatments. Herein, polyethylene glycol （PEG）-modified cobalt sulfide nanosheets （CoS-PEG NSs） are synthesized and unitized as a powerful theranostic nanoagent for efficient photothermal conversion and multimodal imaging for the first time. We demonstrate that the obtained CoS-PEG NSs show excellent compatibility and stability in water and various physiological solutions, and can be effectively inter- nalized by cells, but exhibit a low cytotoxicity. The CoS-PEG NSs exhibit an efficient photothermal conversion capacity, benefited from the strong near-infrared （NIR） absorption, high photothermal conversion efficiency （~ 33.0%）, and excellent photo- thermal stability. Irnportant136 the highly effective photothermal killing effect on cancer ceils after exposure to CoS-PEG NSs plus laser irradiation has been con- firmed by both the standard Cell Counting Kit-8 and live-dead cell staining assays, revealing a concentration-dependent photothermal therapeutic effect. Moreover, utilizing the strong NIR absorbance together with the T2-MR contrast ability of the CoS-PEG NSs, a high-contrast triple-modal imaging, i.e., photoacoustic （PA）, infrared thermal （IRT）, and magnetic resonance （MR） imaging, can be achieved, suggesting a great potential for multimodal imaging to provide comprehensive cancer diagnosis. Our work introduces the first bioapplication of the CoS-PEG nanomaterial as a potential theranostic nanoplatform and may promote further rational design of CoS-based nanostructures for precise/effident cancer diagnosis and therapy.

A ROS-responsive,self-immolative and self-reporting hydrogen sulfide donor with multiple biological activities for the treatment of myocardial infarction

Myocardial infarction(MI),as one of the leading causes of global death,urgently needs effective therapies.Recently,hydrogen sulfide(H2S)has been regarded as a promising therapeutic agent for MI,while its spatiotemporally controlled delivery remains a major issue limiting clinical translation.To address this limitation,we designed and synthesized a novel H2S donor(HSD-R)that can produce H2S and emit fluorescence in response to reactive oxygen species(ROS)highly expressed at diseased sites.HSD-R can specifically target mitochondria and provide red fluorescence to visualize and quantify H2S release in vitro and in vivo.Therapeutically,HSD-R significantly promoted the reconstruction of cardiac structure and function in a rat MI model.Mechanistically,myocardial protection is achieved by reducing cardiomyocyte apoptosis,attenuating local inflammation,and promoting angiogenesis.Furthermore,inhibition of typical pro-apoptotic genes(Bid,Apaf-1,and p53)played an important role in the anti-apoptotic effect of HSD-R to achieve cardioprotection,which were identified as new therapeutic targets of H2S against myocardial ischemia injury.This ROS-responsive,self-immolative,and fluorescent H2S donor can serve as a new theranostic agent for MI and other ischemic diseases.

A novel clustered SPIO nanoplatform with enhanced magnetic resonance T2 relaxation rate for micro-tumor detection and photothermal synergistic therapy

Construction of micro tumor sensitive theranostic nanoagents that can increase the accuracy of imaging diagnosis and boost the therapeutic efficacy has been demonstrated for a promising approach for diagnosis and treatment of cancer.Herein,we reported a novel super-paramagnetic iron oxide(SPIO)based nanoplatform that possess significantly enhanced magnetic resonance property and photothermal effect for tumor theranostic purpose.This polyethylene glycol with four phenylboronic acid(PEG-B4)/CNTs@porphyrin(ph)/SPIO(BCPS)nanoplatform was simply prepared via integrated SPIO,ph,and a novel dendrimer with PEG liner and four PBA groups(PEG-B4)on the surface of carbon nanotubes(CNTs).Subsequently,a significant T2 relaxation rate enhanced can be achieved by the reduced accessibility of water to SPIO clustering.Moreover,the synergetic enhanced photothermal from BCPS nanoplatform contributed to better photothermal effect for cancer therapy.Furthermore,the targeting ability to sialic acid overexpressed tumor was further introduced from phenylboronic acid from PEG-B4.We showed that BCPS nanoplatform could not only selectively identify solid tumors and detect micro-sized metastatic tumor(1 mm)in the liver,but also effectively ablate tumors in a xenograft model,thereby achieving a complete cure rate of 100%at low laser dose.Our results highlight the potential of BCPS nanoplatform for accurate micro-tumor diagnosis and effective tumor therapy.