Advanced Functional Structure‐Based Sensing and Imaging Strategies for Cancer Detection: Possibilities,Opportunities, Challenges,and Prospects

Cancer is the second most common cause of death in the world. The principal limitations thus far encountered in the clinical practice of probing cancer are diverse and include low sensitivity, time consumption, bulkiness, and cost. In this respect, nanomaterial (NM)‐based sensing techniques are recognized as a superior alternative to efficiently resolve such limitations. A better understanding of NM‐based sensing platforms is thus important so that these novel avenues can easily be explored for clinical applications. These platforms have the merits of high sensitivity, high specificity, rapid response, and easy‐to‐read signals. This review offers a comprehensive survey of NM‐based advanced cancer‐sensing techniques and will help the scientific community establish optimum sensing strategies based on an accurate assessment of the interactions between cancer biomarkers and NM‐based platforms.     

Multifunctional Mesoporous Silica Nanoparticles for Cancer‐Targeted and Controlled Drug Delivery

Multifunctional mesoporous silica nanoparticles are developed in order to deliver anticancer drugs to specific cancer cells in a targeted and controlled manner. The nanoparticle surface is functionalized with amino‐β‐cyclodextrin rings bridged by cleavable disulfide bonds, blocking drugs inside the mesopores of the nanoparticles. Poly(ethylene glycol) polymers, functionalized with an adamantane unit at one end and a folate unit at the other end, are immobilized onto the nanoparticle surface through strong β‐cyclodextrin/adamantane complexation. The non‐cytotoxic nanoparticles containing the folate targeting units are efficiently trapped by folate‐receptor‐rich HeLa cancer cells through receptormmediated endocytosis, while folate‐receptor‐poor human embryonic kidney 293 normal cells show much lower endocytosis towards nanoparticles under the same conditions. The nanoparticles endocytosed by the cancer cells can release loaded doxorubicin into the cells triggered by acidic endosomal pH. After the nanoparticles escape from the endosome and enter into the cytoplasm of cancer cells, the high concentration of glutathione in the cytoplasm can lead to the removal of the β‐cyclodextrin capping rings by cleaving the pre‐installed disulfide bonds, further promoting the release of doxorubicin from the drug carriers. The high drug‐delivery efficacy of the multifunctional nanoparticles is attributed to the co‐operative effects of folate‐mediated targeting and stimuli‐triggered drug release. The present delivery system capable of delivering drugs in a targeted and controlled manner provides a novel platform for the next generation of therapeutics.     

电磁照射与人体健康

目前公众越来越关注电磁照射对自身健康的影响,特别是电磁照射致癌以及通信基站安全问题.本文将根据今年来国际组织(WHO、ICNIRP等)对于相关课题的研究,介绍相关的研究结果.     

Drosha蛋白在胰腺癌组织中的表达及其临床意义

目的:探讨胰腺癌组织中Drosha蛋白表达状况及其临床意义。方法:收集胰腺癌样本85例及对应癌旁组织53例,采用HE和免疫组化法检测胰腺癌组织标本中Drosha蛋白的表达并分析其与临床病理因素之间的关系。采用定量PCR方法检测Drosha基因表达。结果:胰腺癌组织中Drosha的表达阳性率为72.9%(62/85),而相应癌旁Drosha表达阳性率为100%(53/53),两者表达差异有统计学意义(P=0.000),Drosha蛋白在胰腺癌中的阳性强度平均积分值由10.3分降至2.3分。Drosha蛋白的表达与肿瘤的分期(c2=19.2,P=0.0003)、分级(c2=10.8,P=0.013)、淋巴结转移(c2=23.6,P=0.00003)等密切相关。与对应癌旁组织相比,Drosha基因在胰腺癌组织中表达下调(P=0.000)。结论:Drosha蛋白在胰腺癌组织中表达下降,Drosha可能在胰腺癌的发生、发展中具有重要作用。     

A Molecular Brush Approach to Enhance Quantum Yield and Suppress Nonspecific Interactions of Conjugated Polyelectrolyte for Targeted Far‐Red/Near‐Infrared Fluorescence Cell Imaging

A red‐fluorescent conjugated polyelectrolyte (CPE, P2 ) is grafted with dense poly(ethylene glycol) (PEG) chains via click chemistry and subsequently modified with folic acid to form a molecular brush based cellular probe ( P4 ). P4 self‐assembles into a core–shell nanostructure in aqueous medium with an average size of 130 nm measured by laser light scattering. As compared to P2 , P4 possesses not only a substantially higher quantum yield (11%), but also reduced nonspecific interactions with biomolecules in aqueous medium due to the shielding effect of PEG. In conjunction with its high photostability and low cytotoxicity, utilization of P4 as a far‐red/near‐infrared cellular probe allows for effective visualization and discrimination of MCF‐7 cancer cells from NIH‐3T3 normal cells in a high contrast, selective, and nonviral manner. This study thus demonstrates a flexible molecular brush approach to overcome the intrinsic drawbacks of CPEs for advanced bioimaging applications.     

Black Phosphorus Quantum Dots Encapsulated Biodegradable Hollow Mesoporous MnO2: Dual-Modality Cancer Imaging and Synergistic Chemo-Phototherapy

To achieve an accurate diagnosis and efficient tumor treatment, developing a facile and powerful strategy to build multifunctional nanotheranostics is highly desirable. Benefiting from the distinct characteristics of black phosphorus quantum dots (BPQDs), herein, a versatile nanoprobe (H-MnO₂/DOX/BPQDs) is constructed for dual-modality cancer imaging and synergistic chemo-phototherapy. The hollow mesoporous MnO₂ (H-MnO₂) nanoparticles are sequentially decorated with a cationic polymer poly (allylamine hydrochloride) (PAH) and an anionic polymer poly (acrylic acid) (PAA). The obtained H-MnO₂-PAH-PAA is covalently grafted with BPQDs-PEG-NH₂ via a carbodiimide cross-linking reaction and then loaded with anti-cancer drug DOX to form final nanoprobe H-MnO₂/DOX/BPQDs. Under the tumor microenvironment, H-MnO₂/DOX/BPQDs is degraded to release encapsulated functional molecules DOX and BPQDs. DOX acts as the chemotherapy and fluorescence imaging agent, and BPQDs endows the nanoprobe with photodynamic therapy (PDT) and photothermal therapy (PTT) abilities under dual laser irradiation of 630 and 808 nm. H-MnO₂ offers contrasts for magnetic resonance imaging (MRI) and facilitates conversion of endogenous H₂O₂ to oxygen, thereby relieving tumor hypoxia and enhancing PDT efficacy. All in vitro and in vivo results demonstrate that the designed nanoprobe displays dual-modality MRI/FL imaging and synergistic chemotherapy/PDT/PTT, which ultimately enhances the accuracy of cancer diagnosis and therapeutic performance.     

人体组织拉曼光谱研究进展

介绍了拉曼光谱测量技术在人体皮肤、血液、乳腺、胃、肺等组织疾病诊断中的研究概况,同时介绍了拉曼测量新技术的发展概况,展望了它的发展前景.     

A Biodegradable Antigen Nanocapsule Promotes Anti-Tumor Immunity via the cGAS-STING Pathway

Materials-based antigen delivery systems can augment the immune response by improving antigen uptake in antigen-presenting cells, targeting lymph nodes, prolonging antigen exposure, enhancing cross-presentation, etc. Recent research revealed that some antigen carriers activate the innate immune pathways without additional adjuvant. Here, a vaccine delivery platform (antigen nanocapsules) constructed by a one-step in situ polymerization is reported, weaving a biodegradable polymer network around the antigen surface. This simple technology allowed us to study the immunomodulatory effect of various antigen carriers. An antigen nanocapsule (NC7) capable of inducing dendritic cell activation and cross-presentation is identified. Further mechanistic studies revealed that NC7 activated the cGAS-STING pathway in a cGAS-dependent manner. Moreover, the subcutaneously injected NC7 accumulated in the lymph nodes and elicited strong cytotoxic T cell immunity and T cell memory against established cancer. Collectively, the often-neglected immunomodulatory effect of various cationic antigen carriers, enabling potential application in cancer vaccines, is uncovered.     

Disrupting Intracellular Iron Homeostasis by Engineered Metal-Organic Framework for Nanocatalytic Tumor Therapy in Synergy with Autophagy Amplification-Promoted Ferroptosis

Metal-organic frameworks (MOFs) featuring good biocompatibility and tunable microstructures are developed to generate reactive oxygen species (ROS) for nanocatalytic therapy. However, the relatively low catalytic activity of MOF and intracellular ion homeostasis, a self-protective mechanism to resist the intracellular accumulation of metal ions, results in the undesirable efficacy of tumor therapy. Herein, a therapeutic strategy is introduced of breaking intracellular iron homeostasis for nanocatalytic therapy in synergy with autophagy amplification-promoted ferroptosis, based on etched MOF nanocatalyst (denoted COS@MOF), which is self-etched by thiamine pyrophosphate (TPP) and further modified with autophagy agonist chitosan oligosaccharides (COS). Such self-etched MOF exhibit an open cavity structure that is more conducive to adsorbing reactive molecules and producing more active sites, and an enhanced Fe(II)/Fe(III) ratio, reinforcing catalytic activity for ROS generation. The catalytic process of COS@MOF can be accelerated by overexpressed endogenous hydrogen sulfide (H₂S) within colorectal tumors which reduces Fe³⁺ into more active Fe²⁺. In vitro and in vivo results demonstrate that COS@MOF amplifies autophagy to break iron homeostasis for facilitating ROS production to promote ferroptosis, achieving synergetic nanocatalytic/ferroptosis tumor therapy. This study provides a promising paradigm to elevate MOF-based catalytic performance in synergy with autophagy amplification-promoted ferroptosis for enhanced therapeutic efficacy.