Polyethylene glycol phospholipids encapsulated silicon 2,3-naphthalocyanine dihydroxide nanoparticles (SiNcOH-DSPEPEG(NH2) NPs) for single NIR laser induced cancer combination therapy

Currently, the combination of photothermal therapy (PTT) and photodynamic therapy (PDT) has emerged as a powerful technique for cancer treatment. However, most examples of combined PTT and PDT reported use multi-component nanocomposites under excitation of separate wavelength, resulting in complex treatment process. In this work, a novel theranostic nanoplatform (SiNcOH-DSPE-PEG(NH₂) NPs) has been successfully developed by coating silicon 2,3-naphthalocyanine dihydroxide (SiNcOH) with DSPE-PEG and DSPE-PEG-NH₂ for photoacoustic (PA) imaging-guided PTT and PDT tumor ablation for the first time. The as-prepared single-agent SiNcOH-DSPE-PEG(NH₂) NPs not only have good water solubility and biocompatibility, but also exhibit high photothermal conversion efficiency and singlet oxygen generation capability upon 808 nm NIR laser irradiation. In addition, owing to their high absorption at NIR region, the SiNcOH-DSPE-PEG(NH₂) NPs can also be employed as an effective diagnostic nanoagent for photoacoustic (PA) imaging. In vitro and in vivo experimental results clearly indicated that the simultaneously combined PTT and PDT under the guidance of PA imaging with single NIR laser excitation can effectively kill cancer cells or eradicate tumor tissues. Taking facile synthesis and high efficiency in cancer treatment by SiNcOH-DSPE-PEG(NH₂) NPs into consideration, our study provides a promising strategy to realize molecular imaging-guided combination therapy.     

纳米荧光探针用于核酸分子的检测及成像研究

核酸,包括脱氧核糖核酸和核糖核酸,在生物的生长、发育、突变、炎症、癌症等正常或异常的生命活动中发挥着重要的作用,它们的异常表达与多种疾病的发生、发展也密切相关.因此,发展准确、有效的方法实现核酸分子的检测,对深入探究核酸的功能调控以及相关疾病的早期检测与治疗都具有重要的意义.荧光检测法与荧光成像技术具有灵敏度高、时空分辨率高等优点,为实时、准确的检测核酸分子提供了有力的工具.本文着重综述了近年来发展的纳米荧光探针用于疾病相关核酸分子的检测与细胞和活体成像工作的研究进展,最后提出了进一步构建新型纳米荧光探针用于核酸检测面临的挑战、未来发展方向与展望.     

Solvent effect in polymer analysis by MALDI-TOF mass spectrometry

Solvent effect is one of the important factors in sample preparation which may affect matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectra of synthetic polymers. MALDI imaging, a useful imaging tool for discovering biomarkers in tissues, is applied here for better comprehension of solvent effect in polymer analysis by MALDI-TOF mass spectrometry. Nylon-6 was chosen as a model polymer for the study of solvent effect. Its MALDI mass spectra in different solvents were performed. MALDI imaging analysis was performed for studying the incorporation of analytes into matrix crystals in different solvent combinations. Specifically, the colocalization of matrix and analyte was obtained through Pearson’s correlation (PC) coefficient analysis of their MALDI images. The results demonstrated that satisfactory spectra were obtained in higher PC value conditions. PC decreased along with an increase in the ratio of poor solvent, which suggested that we should minimize the poor solvent ratio to obtain better MALDI spectra.     

特异性识别半胱氨酸荧光探针的合成及细胞成像研究

基于光诱导电子转移(PET)机制,利用Cys亲核性较强,能够与探针分子发生亲核取代反应,使丙烯酰基离去,使探针分子体系内PET过程失效,合成了一种特异性识别半胱氨酸的荧光探针。当向探针溶液分别加入多种测试物时,除与Cys结构类似的Hcy和GSH会引起探针溶液微弱的荧光变化外,其他氨基酸均不会引起探针溶液荧光强度的变化,该探针对Cys具有良好的选择性和灵敏度,可在生理条件下检测Cys,并且区分Hcy和GSH。同时,该探针成功实现了细胞内Cys的荧光成像,为在生物学及医学中的实际应用建立了一种特异性识别Cys的分析方法。     

Conjugated Polymer Nanoparticles with Appended Photo‐Responsive Units for Controlled Drug Delivery,Release, and Imaging

Carriers that can afford tunable physical and structural changes are envisioned to address critical issues in controlled drug delivery applications. Herein, photo‐responsive conjugated polymer nanoparticles (CPNs) functionalized with donor–acceptor Stenhouse adduct (DASA) and folic acid units for controlled drug delivery and imaging are reported. Upon visible‐light (λ=550 nm) irradiation, CPNs simultaneously undergo structure, color, and polarity changes that release encapsulated drugs into the cells. The backbone of CPNs favors FRET to DASA units boosting their fluorescence. Notably, drug‐loaded CPNs exhibit excellent biocompatibility in the dark, indicating perfect control of the light trigger over drug release. Delivery of both hydrophilic and hydrophobic drugs with good loading efficiency was demonstrated. This strategy enables remotely controlled drug delivery with visible‐light irradiation, which sets an example for designing delivery vehicles for non‐invasive therapeutics.     

Synthesis of a Near‐Infrared BODIPY Dye for Bioimaging and Photothermal Therapy

The development of robust photothermal agents for near‐infrared (NIR) imaging is a great challenge. Herein, we report the design and synthesis of a new photothermal agent, based on the aza‐boron‐dipyrromethene framework (azaBDP). This compound possessed excellent photostability and high photothermal‐conversion efficiency (50 %) under NIR laser irradiation. When the photothermal properties of this compound were utilized for tumor inhibition, stable long‐term fluorescence was observed in living animals. Photothermal treatment efficiently suppressed tumor growth, as evidenced by in vitro and in vivo experiments. Furthermore, NIR emission could be detected by using an imaging system and therapeutic self‐monitoring was achieved by using NIR imaging.     

Bifunctional Fluorescent Probe for Sequential Sensing of Thiols and Primary Aliphatic Amines in Distinct Fluorescence Channels

Thiols and primary aliphatic amines (PAA) are ubiquitous and extremely important species in biological systems. They perform significant interplaying roles in complex biological events. A single fluorescent probe differentiating both thiols and PAA can contribute to understanding the intrinsic inter‐relationship of thiols and PAA in biological processes. Herein, we rationally constructed the first fluorescent probe that can respond to thiols and PAA in different fluorescence channels. The probe exhibited a high selectivity and sensitivity to thiols and PAA. In addition, it displayed sequential sensing ability when the thiols and PAA coexisted. The application experiments indicated that the probe can be used for sensing thiols and PAA in human blood serum. Moreover, the fluorescence imaging of endogenous thiols and PAA as well as antihypertensive drugs captopril and amlodipine in living cells were successfully conducted.     

Near‐Infrared Fluorescent Molecular Probe for Sensitive Imaging of Keloid

Early detection of skin diseases is imperative for their effective treatment. However, fluorescence molecular probes that allow this are rare. The first activatable near‐infrared (NIR) fluorescent molecular probe is reported for sensitive imaging of keloid cells, skin cells from abnormal scar fibrous lesions. As keloid cells have high expression levels of fibroblast activation protein‐alpha (FAPα), the probe (FNP1) is designed to have a caged NIR dye and a FAPα‐cleavable peptide substrate linked by a self‐immolative segment. FNP1 can quickly and specifically turn on its fluorescence at 710 nm by 45‐fold in the presence of FAPα, allowing it to effectively recognize keloid cells from normal skin cells. Integration of FNP1 with a simple microneedle‐assisted topical application enables sensitive detection of keloid cells in metabolically‐active human skin tissue with a theoretical limit of detection down to 20 000 cells.     

Imaging of Colorectal Cancers Using Activatable Nanoprobes with Second Near‐Infrared Window Emission

Fluorescent probes in the second near‐infrared window (NIR‐II) allow high‐resolution bioimaging with deep‐tissue penetration. However, existing NIR‐II materials often have poor signal‐to‐background ratios because of the lack of target specificity. Herein, an activatable NIR‐II nanoprobe for visualizing colorectal cancers was devised. This designed probe displays H₂S‐activated ratiometric fluorescence and light‐up NIR‐II emission at 900–1300 nm. By using this activatable and target specific probe for deep‐tissue imaging of H₂S‐rich colon cancer cells, accurate identification of colorectal tumors in animal models were performed. It is anticipated that the development of activatable NIR‐II probes will find widespread applications in biological and clinical systems.     

Super‐Chelators for Advanced Protein Labeling in Living Cells

Live‐cell labeling, super‐resolution microscopy, single‐molecule applications, protein localization, or chemically induced assembly are emerging approaches, which require specific and very small interaction pairs. The minimal disturbance of protein function is essential to derive unbiased insights into cellular processes. Herein, we define a new class of hexavalent N‐nitrilotriacetic acid (hexaNTA) chelators, displaying the highest affinity and stability of all NTA‐based small interaction pairs described so far. Coupled to bright organic fluorophores with fine‐tuned photophysical properties, the super‐chelator probes were delivered into human cells by chemically gated nanopores. These super‐chelators permit kinetic profiling, multiplexed labeling of His₆‐ and His₁₂‐tagged proteins as well as single‐molecule‐based super‐resolution imaging.