Smart Nanodrug with Nuclear Localization Sequences in the Presence of MMP-2 To Overcome Biobarriers and Drug Resistance

A series of physiological barriers have impeded nanoparticle-based drug formulations (NDFs) from reaching their targeted sites and achieving therapeutic outcomes. In this study, we develop size-controllable stealth doxorubicin-loaded nanodrug coated with CD47 peptides (DOX/sNDF-CD47) based on supramolecular chemistry to overcome multiple biological barriers. The smart DOX/sNDF-CD47 can efficiently decrease sequestration by macrophages and disassemble into poly(amidoamine) dendrimers with nuclear localization sequences (DOX/PAMAM-NLS) in the presence of matrix metalloproteinase-2 (MMP-2). Such structure transformation endows DOX/sNDF-CD47 with the ability of deep penetration in multicellular tumor spheroid, lysosomal escape, and nucleus localization, resulting in excellent cytotoxicity and drug resistance combating. In vivo experiments further confirmed that DOX/sNDF-CD47 has good tumor-targeting ability and can significantly improve therapeutic efficacy of DOX on xenograft tumor model. The ability to overcome multiple biological barriers makes sNDF-CD47 a promising NDFs to treat cancer expressing MMP-2 and combating drug resistance.     

功能化金属-有机框架材料在肿瘤治疗中的研究进展

恶性肿瘤由于其易转移、复发等特点，已经严重危害到人类的生命健康.近年来，研究人员设计了大量纳米药物载体，将抗肿瘤药物安全有效地运载到肿瘤，有效地提高了药效并降低了毒副作用.金属有机框架材料（metal-organic frameworks，MOFs）是一类有序、多孔的晶态材料，具有比表面积大、结构可设计性强、易生物降解等独特优势，已经被广泛应用于气体吸附与分离、催化、药物传递、生物大分子固载以及肿瘤治疗等方面.目前，基于MOFs的生物医用研究主要集中在MOF材料的可控合成，表面修饰，基于MOF独特理化性质发展的多模式成像技术以及肿瘤靶向的药物运载技术等几个方面.主要介绍了基于MOFs构建的生物功能化材料在肿瘤治疗中的应用，并对其在生物医学领域的应用进行了展望.     

Tin,Titanium, Tantalum,Vanadium and Niobium Oxide Based Sensors to Detect Colorectal Cancer Exhalations in Blood Samples

User-friendly, low-cost equipment for preventive screening of severe or deadly pathologies are one of the most sought devices by the National Health Services, as they allow early disease detection and treatment, often avoiding its degeneration. In recent years more and more research groups are developing devices aimed at these goals employing gas sensors. Here, nanostructured chemoresistive metal oxide (MOX) sensors were employed in a patented prototype aimed to detect volatile organic compounds (VOCs), exhaled by blood samples collected from patients affected by colorectal cancer and from healthy subjects as a control. Four sensors, carefully selected after many years of laboratory tests on biological samples (cultured cells, human stools, human biopsies, etc.), were based here on various percentages of tin, tungsten, titanium, niobium, tantalum and vanadium oxides. Sensor voltage responses were statistically analyzed also with the receiver operating characteristic (ROC) curves, that allowed the identification of the cut-off discriminating between healthy and tumor affected subjects for each sensor, leading to an estimate of sensitivity and specificity parameters. ROC analysis demonstrated that sensors employing tin and titanium oxides decorated with gold nanoparticles gave sensitivities up to 80% yet with a specificity of 70%.     

Diffusion with a Discontinuous Potential: a Non-Linear Semigroup Approach

This paper studies existence of mild solution to a sharp cut off model for contact driven tumor growth. Analysis is based on application of the Crandall-Liggett theorem for ω-quasi-contractive semigroups on the Banach space L~1(?). Furthermore,numerical computations are provided which compare the sharp cut off model with the tumor growth model of Perthame, Quirós, and Vázquez [13].     

Natural Polyphenol–Vanadium Oxide Nanozymes for Synergistic Chemodynamic/Photothermal Therapy

The selection of suitable nanozymes with easy synthesis, tumor specificity, multifunction, and high therapeutics is meaningful for tumor therapy. Herein, a facile one-step assembly approach was employed to successfully prepare a novel kind of natural polyphenol tannic acid (TA) hybrid with mixed valence vanadium oxide nanosheets (TA@VO_x NSs). In this system, VO_x is assembled with TA through metal–phenolic coordination interaction to both introduce superior peroxidase-like activity and high near infrared (NIR) absorption owing to partial reduction of vanadium from V⁵⁺ to V⁴⁺. The presence of mixed valence vanadium oxide in TA@VO_x NSs is proved to be the key for the catalytic reaction of hydrogen peroxide (H₂O₂) to ^. OH, and the corresponding catalytic mechanism of H₂O₂ by TA@VO_x NSs is proposed. Benefitting from such peroxidase-like activity of TA@VO_x NSs, the overproduced H₂O₂ of the tumor microenvironment allows the realization of tumor-specific chemodynamic therapy (CDT). As a valid supplement to CDT, the NIR absorption enables TA@VO_x NSs to have NIR light-mediated conversion ability for photothermal therapy (PTT) of cancers. Furthermore, in vitro and in vivo experiments confirmed that TA@VO_x NSs can effectively inhibit the growth of tumors by synergistic CDT/PTT. These results offer a promising way to develop novel vanadium oxide-based nanozymes for enhanced synergistic tumor-specific treatment.     

The new iron(III) 3-oxo-N-(pyridin-2-yl)butanamide complex promotes Ehrlich solid tumor regression in mice via induction of apoptosis

Currently used chemotherapeutic drugs had serious adverse effects e.g. myelo-suppression, anemia and nephrotoxicity. Thus, developing new alternatives is of great importance. We aimed to develop a new prospective antitumor complex combines iron metal ion and 3-oxo-N-(pyridin-2-yl)butanamide ligand that may be effective with less toxicity towards healthy tissues. Anticancer activities of the developed complex were studied in vitro and in vivo using induced Ehrlich solid tumor in mice as animal model. In vitro, the complex (1 mmol/L) exhibited superoxide dismutase (SOD)-like activity of 86.69 %, catalase-like activity of 170 U/100 mL, and 99.06% mortality of Ehrlich ascites carcinoma (EAC) cells. Complex ability to interact with DNA was proved spectrophotometrically. Flow-cytometrically, EAC cells treated with the complex showed higher apoptosis, caspase 3 activity, and p53 compared to the untreated EAC cells. In vivo, the complex showed prominent dose-dependent antitumor activities. It reduced tumor volume and weight, prolonged mice life span, and reversed the hematological indices, malondialdehyde (MDA), total antioxidant capacity (TAC), ALT and urea levels towards normal. Finally, our findings indicate that the complex motivates Ehrlich solid tumor regression in mice via induction of apoptosis. Its effect was better than that of cisplatin.     

恶性肿瘤的传质问题（Ⅱ）——药物传输部分

本文提出肿瘤中药物传输的三重介质模型·基于第（Ⅰ）部分流体动力学的计算结果，采用有限元方法，在不同初始和边界条件下求解了对流—扩散方程组·根据计算结果，详细分析了药物注射方式、分子量、淋巴、药物结合和坏死区等对抗体免疫球蛋白ＩｇＧ及其片断Ｆａｂ在肿瘤中浓度分布的影响·     

Synthesis of the Active Stilbenoids by Photooxidation Reaction of trans-e-Viniferin

Introduction It was reported that stilbene monomers showed multi-faced biological activities, such as antioxidation, antimutagen, antibacterial, antifungal activities.1 Espe-cially, isorhapontigenin and resveratrol showed potent inhibition on biosynthesis of leukotriene and its receptor antagonist.2 Some oligostilbenes exhibited more potent bioactivities than their monomers.3 In recent years, a number of oligostilbenes were isolated from natural sources, but a few of studies on their pharmacol…     

考虑冷热刀刀头温度响应对制定肿瘤治疗计划的影响

本文对冷热联合治疗肿瘤过程中在体生物组织的温度响应进行了深入的数值研究。组织被当作非理想材料,在一定的温度范围内冷冻和融化,并且考虑了未冻结组织和未损伤组织区域的血液灌注及代谢产热的影响。对比考虑和不考虑冷热刀刀头温度响应两种情形的计算结果表明,拟定治疗计划中若不考虑刀头温度响应,则有可能会造成冷热剂量的不足,从而无法彻底杀灭肿瘤。     

Proton nuclear magnetic resonance spectra of brain tumors

Proton nuclear magnetic resonance (NMR) spectra were successfully measured in human brain tumor tissues and experimental rat brain tumors. The investigation was performed on clinical materials which consisted of tissue from one normal brain and 36 brain tumors. Normal rat brain tissue and rat glioma implanted in the brain were also analysed. NMR measurements were carried out at the resonance frequency of 99.54 MHz. The proton NMR spectrum of the normal brain consisted of one broad component and eight superimposed sharp peaks. The sharp peaks obtained from the brain tumors varied from those of the normal brain. A decrease in the signal intensity from N-acetyl aspartate was the most common finding in all tumors. Spectral patterns were similar within the same histological types, but varied among the different types. Therefore, ¹H-NMR spectra might indicate the metabolism characteristic of each tumor type which would be invaluable for clinical differential dagnosis of brain tumors.