Tumor‐Targeting W18O49 Nanoparticles for Dual‐Modality Imaging and Guided Heat‐Shock‐Response‐Inhibited Photothermal Therapy in Gastric Cancer

Photothermal therapy (PTT) is an emerging noninvasive and precise localized therapeutic modality; however, it is deeply limited by its poor tumor accumulation, inadequate photothermal conversion efficiency, and the thermoresistance of cancer cells. Aimed at these shortcomings, tumor‐targeting nanoparticles (iRGD‐W₁₈O₄₉‐17AAG) comprising carboxyl‐group‐functionalized W₁₈O₄₉ nanoparticles, integrin‐targeting peptide iRGD, and HSP90‐inhibitor 17AAG are developed. The W₁₈O₄₉ nanoparticles act as excellent PTT carriers and computed tomography (CT) imaging contrast agents. The ring type polypeptide iRGD promotes the accumulation of nanoparticles in the tumour and further penetration into cancer cells. The introduction of 17AAG can inhibit the heat‐shock response and overcome the thermoresistance, thus increasing the curative effect of PTT and reducing the chance of tumor recurrence. The W₁₈O₄₉ nanoparticles can also be used to monitor and guide the phototherapeutic through CT and near‐infrared fluorescence imaging after modification with Cy5.5. In addition, superior biosafety is also indicated in both preliminary in vitro and in vivo assessments. The potential of iRGD‐W₁₈O₄₉‐17AAG in tumor targeting, dual modality imaging‐guided and remarkable enhanced PTT of gastric cancer with ignorable side effect both in vitro and in vivo, which may be further applied in clinic, is highlighted.     

A Ru(II)-Based Nanoassembly Exhibiting Theranostic PACT Activity in NIR Region

Photoactivated chemotherapy (PACT) has appealing merits over traditional chemotherapy as well as photodynamic therapy (PDT) by virtue of its spatial and temporal control on drug activity and oxygen-independent mechanisms of action. However, the short photoactivation wavelengths, e.g., visible light–activated Ru(II)-based PACT agents, limit the clinical application severely. In this work, a facile construction of supramolecular nanoparticles from a poly(ethylene glycol) (PEG)-modified [Ru(dip)₂(py-SO₃)]⁺ (abbreviated as Ru-PEG, dip = 4,7-diphenyl-1,10-phenanthroline, py-SO₃ = pyridine-2-sulfonate) and 1,3-phenylenebis(pyren-1-ylmethanone) (BP) is shown. While Ru-PEG may undergo photoinduced ligand dissociation and release anticancer species of [Ru(dip)₂(H₂O)₂]²⁺, BP has extremely large two-photon absorption cross sections (δ₂) in the NIR region and intense fluorescence over the wavelengths where Ru-PEG has strong absorption. Thus, two-photon excitation of BP followed by an efficient Förster resonance energy transfer (FRET) from BP to Ru-PEG may lead to a potent inactivation against cisplatin-resistant cancer cells and 3D multicellular tumor spheroids (MCTSs). The residue fluorescence of BP also allows the cellular uptake of the particles to be visualized. This work provides a universal and convenient strategy to realize theranostic PACT in the ideal phototherapeutic window of 650–900 nm.     

Metabolic Tumor Imaging with Rapidly Signal-Enhanced 1-13C-Pyruvate-d3

The metabolism of malignant cells differs significantly from that of healthy cells and thus, it is possible to perform metabolic imaging to reveal not only the exact location of a tumor, but also intratumoral areas of high metabolic activity. Herein, we demonstrate the feasibility of metabolic tumor imaging using signal-enhanced 1-¹³C-pyruvate-d₃, which is rapidly enhanced via para-hydrogen, and thus, the signal is amplified by several orders of magnitudes in less than a minute. Using as a model, human melanoma xenografts injected with signal-enhanced 1-¹³C-pyruvate-d3, we show that the conversion of pyruvate into lactate can be monitored along with its kinetics, which could pave the way for rapidly detecting and monitoring changes in tumor metabolism.     

Advances in Targeting Drug Biological Carriers for Enhancing Tumor Therapy Efficacy

Chemotherapy drugs continue to be the main component of oncology treatment research and have been proven to be the main treatment modality in tumor therapy. However, the poor delivery efficiency of cancer therapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. The recent integration of biological carriers and functional agents is expected to camouflage synthetic biomimetic nanoparticles for targeted delivery. The promising candidates, including but not limited to red blood cells and their membranes, platelets, tumor cell membrane, bacteria, immune cell membrane, and hybrid membrane are typical representatives of biological carriers because of their excellent biocompatibility and biodegradability. Biological carriers are widely used to deliver chemotherapy drugs to improve the effectiveness of drug delivery and therapeutic efficacy in vivo, and tremendous progress is made in this field. This review summarizes recent developments in biological vectors as targeted drug delivery systems based on microenvironmental stimuli-responsive release, thus highlighting the potential applications of target drug biological carriers. The review also discusses the possibility of clinical translation, as well as the exploitation trend of these target drug biological carriers.     

血液中循环肿瘤细胞捕获与释放方法研究进展

血液中的循环肿瘤细胞(CTCs)与癌症转移密切相关,对CTCs进行检测有利于实现癌症早期诊断。但由于血液中CTCs个数稀少且存在异质性,因此急需发展血液中CTCs的高效分离及检测方法。此外,释放被捕获的细胞并进行后续培养及基因水平分析,将会进一步推进癌症的个性化治疗。本文综述了近年来CTCs捕获及释放的相关研究进展,并展望了其应用前景及发展方向。     

Far‐Red and Near‐IR AIE‐Active Fluorescent Organic Nanoprobes with Enhanced Tumor‐Targeting Efficacy: Shape‐Specific Effects

The rational design of high‐performance fluorescent materials for cancer targeting in vivo is still challenging. A unique molecular design strategy is presented that involves tailoring aggregation‐induced emission (AIE)‐active organic molecules to realize preferable far‐red and NIR fluorescence, well‐controlled morphology (from rod‐like to spherical), and also tumor‐targeted bioimaging. The shape‐tailored organic quinoline–malononitrile (QM) nanoprobes are biocompatible and highly desirable for cell‐tracking applications. Impressively, the spherical shape of QM‐5 nanoaggregates exhibits excellent tumor‐targeted bioimaging performance after intravenously injection into mice, but not the rod‐like aggregates of QM‐2.     

Fluorescent In Situ Targeting Probes for Rapid Imaging of Ovarian‐Cancer‐Specific γ‐Glutamyltranspeptidase

γ‐Glutamyltranspeptidase (GGT) is a tumor biomarker that selectively catalyzes the cleavage of glutamate overexpressed on the plasma membrane of tumor cells. Here, we developed two novel fluorescent in situ targeting (FIST) probes that specifically target GGT in tumor cells, which comprise 1) a GGT‐specific substrate unit (GSH), and 2) a boron–dipyrromethene (BODIPY) moiety for fluorescent signalling. In the presence of GGT, sulfur‐substituted BODIPY was converted to amino‐substituted BODIPY, resulting in dramatic fluorescence variations. By exploiting this enzyme‐triggered photophysical property, we employed these FIST probes to monitor the GGT activity in living cells, which showed remarkable differentiation between ovarian cancer cells and normal cells. These probes represent two first‐generation chemodosimeters featuring enzyme‐mediated rapid, irreversible aromatic hydrocarbon transfer between the sulfur and nitrogen atoms accompanied by switching of photophysical properties.     

基于i-motif的生物医学应用纳米系统:pH成像、药物控释和肿瘤诊疗

I-motif作为一种新型pH敏感元件,因其在不同pH条件下可以进行快速的构象转变,以及具有自动化合成、优异的生物相容性和灵活的功能化整合等优点,在生物医学领域引起了广泛的关注和研究热潮。该文介绍了i-motif的基本性能,综述了基于i-motif的纳米系统在细胞pH成像、pH控制的药物释放和pH响应型肿瘤诊疗一体化等生物医学领域的应用研究进展,总结了基于i-motif的纳米系统在生物医学应用中面临的挑战,并展望了基于i-motif的纳米系统在精准医学中的应用前景。     

基于酶循环放大的DNA生物传感器用于检测食管鳞状细胞癌生物标志物蛋白PDGF-BB

食管鳞状细胞癌（ESCC）患者发病早期由于体内的肿瘤标志物种类少且含量低,难以在患病早期发现疾病从而快速反应并有效治疗。因此,找到一种合适的标志物对其进行快速高效检测是研究者亟待解决的问题。血小板衍生生长因子（PDGF－BB）在恶性肿瘤的早期诊断中具有极其重要的地位。该文基于酶循环放大荧光光谱设计了一种用于PDGF－BB检测的DNA生物传感器,利用特定位点剪切酶,实现了信号放大,检出限由1 fmol/L降至1 amol/L,大大提高了检测的灵敏度。该方法通过检测血液中PDGF－BB浓度,从而实现对ESCC的简单、快速、高效诊断,在生物化学和医学应用上具有重要价值。     

Synthesis and characterization of folic acid‐modified carboxymethyl chitosan‐ursolic acid targeted nano‐drug carrier for the delivery of ursolic acid and 10‐hydroxycamptothecin

Carboxymethyl chitosan (CMCS), as a water‐soluble, biocompatible, and biodegradable polymer, is an excellent carrier for a sustained drug delivery system. In this study, a amphiphilic carboxymethyl chitosan‐ursolic acid nano‐drug carrier modified by folic acid (FPCU) were prepared, and then the nano‐drug carrier wrapped another anticancer drug 10‐hydroxycamptothecin were self‐assembled into nanoparticles (FPCU/HCPT NPs). The FPCU/HCPT NPs had a suitable size, high drug loading efficiency of ursolic acid (6.4%) and 10‐hydroxycamptothecin (14.1%). The drug release study in vitro indicated that the nanoparticles have obviously sustained effect and pH sensitive behaviors, the drug release amount was higher at pH 5.5 than at pH 7.4. in vitro and in vivo study showed that the nanoparticles displayed a high antitumor efficiency to tumor cells compared with free drug. The nano delivery system as a carrier for ursolic acid (UA) and 10‐hydroxycamptothecin (HCPT) has good application prospects in cancer treatment.