新型四酰胺基铝酞菁的制备及其在体光动力抗癌活性研究

为寻求在红光区具有良好光动力治疗（PDT）抗癌活性的新型四取代铝酞菁光敏剂，以4-硝基邻苯二甲酸为原料，用苯酐尿素法合成了四氨基铝酞菁（TAAIPc）、四乙酰胺基铝酞菁（TAcAAIPc）、四丙酰胺基铝酞菁（TPrAAIPc）和四丁酰胺基铝酞菁（TBuAAIPc）。表征了所得产物的结构，测试了其荧光光谱和急性毒性；并在输出波长532nm下测定了其光动力抗癌活性。结果表明，所得的酰胺基取代系列铝酞菁对小鼠无明显毒性。当注射剂量为20mg／kg时，上述四种铝酞菁光敏剂对小鼠S180实体瘤的抑瘤率分别为44．96％，45．87％．45．62％和48．65％，差别不明显。加大剂量至40mg／kg时，抑瘤率依次为39．16％，42．81％，40．56％和51．82％。在此剂量下，四丁酰胺基铝酞菁表现出较高的光动力治疗抗癌活性。     

Cancer Stem Cell‐Platelet Hybrid Membrane‐Coated Magnetic Nanoparticles for Enhanced Photothermal Therapy of Head and Neck Squamous Cell Carcinoma

Cell membrane–based nanosystems with desirable characteristics have been studied extensively for many therapeutic applications. However, current research has focused on single cell membrane, and multifunctional fused membrane materials from different membrane types are still rare. Herein, a platelet–cancer stem cell (CSC) hybrid membrane‐coated iron oxide magnetic nanoparticle (MN) {[CSC‐P]MN} is presented for the first time for the enhanced photothermal therapy of head and neck squamous cell carcinoma (HNSCC). Inherited from the original source cells, the platelet membrane shows immune evading ability due to the surface marker comprising a number of “don't eat me” signals, and the CSC membrane has homotypic targeting capabilities due to the specific surface adhesion molecules. The [CSC‐P]MNs possess superior characteristics for immune evasion, active cancer targeting, magnetic resonance imaging, and photothermal therapy. Compared with single cell membrane–coated MNs, [CSC‐P]MNs exhibit prolonged circulation times and enhanced targeting abilities. Moreover, the [CSC‐P]MNs exhibit a superior photothermal ability that provides excellent HNSCC tumor growth inhibition, particularly in an immunocompetent Tgfbr1/Pten conditional double knockout HNSCC mouse model that contains a more complex tumor microenvironment that is similar to the human HNSCC microenvironment. Collectively, this biomimetic multimembrane‐coated nanoplatform may provide enhanced antitumor efficacy in the complex tumor microenvironment.     

Coordinating Biointeraction and Bioreaction of a Nanocarrier Material and an Anticancer Drug to Overcome Membrane Rigidity and Target Mitochondria in Multidrug‐Resistant Cancer Cells

Multidrug resistance (MDR) is a main cause of chemotherapy failure in cancer treatment. It is associated with complex cellular and molecular mechanisms including overexpression of drug efflux transporters, increased membrane rigidity, and impaired apoptosis. Numerous efforts have been made to overcome efflux transporter‐mediated MDR using nanotechnology‐based approaches. However, these approaches fail to surmount plasma membrane rigidity that attenuates drug penetration and nanoparticle endocytosis. Here, a “one‐two punch” nanoparticle approach is proposed to coordinate intracellular biointeraction and bioreaction of a nanocarrier material docosahexaenoic acid (DHA) and an anticancer prodrug mitomycin C (MMC) to enhance mitochondrion‐targeted toxicity. Incorporation of DHA in solid polymer‐lipid nanoparticles first reduces the membrane rigidity in live cancer cells thereby increasing nanoparticle cellular uptake and MMC accumulation. Subsequent intracellular MMC bioreduction produces free radicals that in turn react with adjacent DHA inducing significantly elevated mitochondrial lipid peroxidation, leading to irreversible damage to mitochondria. Preferential tumor accumulation of the nanoparticles and the synergistic anticancer cytotoxicity remarkably inhibit tumor growth and prolonged host survival without any systemic toxicity in an orthotopic MDR breast tumor model. This work suggests that combinatorial use of biophysical and biochemical properties of nanocarrier materials with bioreactive prodrugs is a powerful approach to overcoming multifactorial MDR in cancer.     

AFM观察稳恒磁场对细胞表面精细结构的影响

利用原子力显微镜(AFM)观察稳恒磁场(SMF)处理后,悬浮生长细胞(K562人白血病细胞)、贴壁生长细胞(人结肠癌SW480细胞)、小鼠肝癌细胞Hepal-6和原代小鼠肝细胞表面精细结构的变化,以了解SMF杀伤肿瘤细胞的可能机制.观察结果显示:随曝磁时间延长,SMF可在肿瘤细胞表面造成不同程度损伤,主要表现为细胞膜上出现许多大小不一的凹陷,且凹陷数量和直径随着曝磁时间延长而增加.与MTT检测相比,AFM观察到的各类细胞表面损伤远早于细胞的生长抑制.实验观察显示,悬浮生长细胞比贴壁生长细胞对磁场处理更为敏感,小鼠肝癌细胞比肝细胞对磁处理更敏感.实验结果显示,AFM能够及早观察到细胞表面因SMF作用而产生的精细结构方面的变化.     

三种热效应激光汽化兼热杀癌的理论计算与应用方法讨论

本文根据激光汽化兼热杀癌肿瘤的理论模型^[1,2]，对三种常见热效应激光进行了理论计算和结果对比，讨论了在较大汽化域情况下尽可能减少照射治疗时间的应用方法和措施，为激光治疗较大肿瘤提供具体理论参考数据。