低温等离子体对 MCF-7 乳腺癌细胞的 化疗增敏作用

为了改善肿瘤细胞对化疗药物的耐药性,该文提供了一种通过促进细胞对药物的摄取来增敏 化疗的方法。低温等离子体作用肿瘤细胞后,培养基内的活性氧显著升高,进一步改变了细胞膜通透 性,使得外源活性氧及钙离子进入细胞内而诱发细胞凋亡。与此同时,细胞膜通透性的改变还可以增 加细胞对化疗药物的摄取,进一步提高了肿瘤细胞杀伤效率。结果显示,细胞经过等离子体处理以 后,显示出 20% 的细胞杀伤效率。阿霉素作为常见的抗肿瘤药物,在 4 μg/mL 的浓度下可以杀伤 46% 的细胞;而联合等离子体治疗后,细胞杀伤效率增加至 88%,显著增敏了阿霉素的化疗效果。另外, 等离子体联合金纳米棒治疗后,显示出 90% 的细胞杀伤效率,相对于单独使用金纳米棒(64%)的效果 更为显著。因此,等离子体在引发细胞凋亡的同时,可以通过细胞膜通透性的改变,增加细胞对化疗 药物的摄取,进而增敏化疗效果。     

Hierarchically Targeted and Penetrated Delivery of Drugs to Tumors by Size‐Changeable Graphene Quantum Dot Nanoaircrafts for Photolytic Therapy

Theranostic nanohybrids are promising for effective delivery of therapeutic drug or energy and for imaging‐guided therapy of tumors, which is demanded in personalized medicine. Here, a size‐changeable graphene quantum dot (GQD) nanoaircraft (SCNA) that serves as a hierarchical tumor‐targeting agent with high cargo payload is developed to penetrate and deliver anticancer drug into deep tumors. The nanoaircraft is composed of ultrasmall GQDs (less than 5 nm) functionalized with a pH‐sensitive polymer that demonstrates an aggregation transition at weak acidity of tumor environment but is stable at physiological pH with stealth function. A size conversion of the SCNA at the tumor site is further actuated by near‐infrared irradiation, which disassembles 150 nm of SCNA into 5 nm of doxorubicin (DOX)/GQD like a bomb‐loaded jet, facilitating the penetration into the deep tumor tissue. At the tumor, the penetrated DOX/GQD can infect neighboring cancer cells for repeated cell killing. Such a SCNA integrated with combinational therapy successfully suppresses xenograft tumors in 18 d without distal harm. The sophisticated strategy displays the hierarchically targeted and penetrated delivery of drugs and energy to deep tumor and shows potential for use in other tumor therapy.     

绒毛膜癌的研究历程:从协和经验到国际典范

绒毛膜癌是一种高度恶性的妇科肿瘤,侵袭性高,早期可经血行转移至全身而成为全身性疾病。20世纪60年代前,因缺乏有效治疗方法,绒毛膜癌患者死亡率高达90%。1949年以来,在宋鸿钊院士带领下,北京协和医院对绒毛膜癌的发生、发展、诊断与治疗进行了一系列研究,并取得开创性成果。经团队不懈努力,将"死亡率90%以上"反转为"总体治愈率90%以上",极大推动了该领域学术水平的发展。目前我国在该领域研究中仍处于国际领先地位,北京协和医院经验得到国际同行认可并被写入国际指南。     

Iron Oxide Nanoparticles for Magnetically-Guided and Magnetically-Responsive Drug Delivery

In this review, we discuss the recent advances in and problems with the use of magnetically-guided and magnetically-responsive nanoparticles in drug delivery and magnetofection. In magnetically-guided nanoparticles, a constant external magnetic field is used to transport magnetic nanoparticles loaded with drugs to a specific site within the body or to increase the transfection capacity. Magnetofection is the delivery of nucleic acids under the influence of a magnetic field acting on nucleic acid vectors that are associated with magnetic nanoparticles. In magnetically-responsive nanoparticles, magnetic nanoparticles are encapsulated or embedded in a larger colloidal structure that carries a drug. In this last case, an alternating magnetic field can modify the structure of the colloid, thereby providing spatial and temporal control over drug release.     

Safety,Pharmacokinetics and Biodistribution Studies of a β-galactoside Prodrug of Doxorubicin for Improvement of Tumor Selective Chemotherapy

Anthracycline antibiotics, particularly doxorubicin (DOX) and daunorubicin, have been used extensively in the treatment of human malignancies. However, cardiotoxicity and multidrug resistance are significant problems that limit the clinical efficacy of such agents. Rational design to avoid these side effects includes strategies such as drug targeting and prodrug synthesis. The DOX prodrug N-(β-D-glucopyranosylbenzyloxycarbonyl)-doxorubicin (prodrug 1) was synthesized for specific activation by β-galactosidase, which is expected to release in necrotic areas of tumor lesions. Described here is the safety, pharmacokinetics, and biodistribution studies of a β-galactoside prodrug of DOX. In vivo safety evaluation was done in the Ehrlich Ascites Carcinoma (EAC) tumor model. The dose of DOX was 8 mg/kg and the dose of prodrug was 8 mg/kg and 24 mg/kg of DOX equivalents. Our results on cytotoxicity, which demonstrated compression in the number of EAC cells and their viability, substantiate these data. Prodrug 1 was safe up to a dose of 24 mg/kg of DOX equivalents in EAC mice. The pharmacokinetics and biodistribution of prodrug (300 mg/kg) in normal mice were determined and compared with DOX (20 mg/kg). Administration of DOX in normal mice resulted in a peak plasma concentration of 19.45 μM (t = 30 minutes). Prodrug injection resulted in 3- to 16-fold lower concentrations in the tissues of normal mice. As it is more polar, lower levels were observed in tissues and plasma in contrast to the parent compound DOX. In vivo safety studies have shown that prodrug 1 had a maximum tolerated dose compared with DOX and led to improved pharmacokinetics in normal mice.