Monomethyl auristatin E (MMAE) is a derivative of the marine peptide Dolastatin 10, which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials. The antibody drug conjugate (ADC) of MMAE is currently used in clinical practice. However, the safety issues of MMAE-based ADC, such as high drug toxicity and poor bioavailability, still exist when using it for anticancer therapy. A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects. Herein, PLGA-b-PEG2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy. The sustained release effect and the immunogenic cell death (ICD) effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments. The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention (EPR) effect, inducing cell apoptosis and causing a certain degree of immune response. The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC. Overall, this study provides a safe and effective chemotherapeutic approach, as well as a simple and effective synthetic process for MMAE-based nanoparticles, improving their therapeutic efficacy and safety.

光热治疗以其无创性、非侵入性、副作用小等特点受到了广泛关注。二维碳化钛（MXene）作为一种新型纳米材料，具有优异的物理和化学性能，其中包括良好的光热效应。本课题组通过静电吸附作用构建了基于MXene的光热/化疗协同治疗纳米试剂，该纳米试剂具有优异的消光系数［24.05 L/（g·cm）］以及出色的光热转效率（31.34%）。体外细胞实验结果表明该纳米对HepG2细胞起到了良好的抑制效果，经其治疗后的细胞存活率仅为21.09%。

针对口服给药体系如何保护药物分子免受人体内环境影响这一挑战, 采用乳化凝胶法设计合成了一种pH值敏感性的海藻酸钠(SA)-蒙脱石(MMT)复合微球MMT/SA, 用以负载抗癌药物盐酸阿霉素(DOX), 在保护药物分子的同时克服了胃肠道的生物化学屏障。探索了MMT处理工艺和合成配比的不同对微球形貌的影响, 最终控制微球尺寸在20 μm以内, 且分布均一。复合载药微球DOX/MMT/SA的载药率为14.7%, 在模拟人工胃液和人工肠液环境中表现出不同的药物缓释效果, 在模拟人工肠液中的累计释放率(31.7%)明显高于在人工胃液中的释放率(15.8%), 且对人结肠癌细胞有明显的杀伤效果。

为了研究血卟啉单甲醚(HMME)介导的光动力抗微生物化疗法(PACT)对牙龈卟啉单胞菌(Porphyromonas gingivalis)的杀菌效果, 采用荧光分光光度计观察HMME光照后产生活性氧的荧光量, 后采用平板菌落计数法检测HMME介导的PACT对牙龈卟啉单胞菌的体外杀菌效果, 并用激光共聚焦显微镜(CLSM)观察各组处理后死活菌的分布情况, 使用电泳光散射法检测HMME与牙龈卟啉单胞菌的zeta电位。结果表明: HMME在光照下主要产生单线态氧(P<0.05), 其介导的PACT组细菌存活率明显下降, 与对照组相比有统计学差异(P<0.05); CLSM观测PACT组发现大量红色荧光, 说明HMME介导PACT可有效杀灭牙龈卟啉单胞菌, HMME与牙龈卟啉单胞菌均为负电位, 影响二者结合。HMME介导的PACT可有效杀灭牙龈卟啉单胞菌, 为PACT应用于临床治疗牙周炎提供了试验依据, 也表明后期需要研发带正电荷的新型光敏剂, 以提高光动力杀菌效果。

Docetaxel-based chemotherapy, as the first-line treatment for metastatic castration-resistant prostate cancer (mCRPC), has succeeded in helping quite a number of patients to improve quality of life and prolong survival time. However, almost half of mCRPC patients are not sensitive to docetaxel chemotherapy initially. This study aimed to establish models to predict sensitivity to docetaxel chemotherapy in patients with mCRPC by using serum surface-enhanced Raman spectroscopy (SERS). A total of 32 mCPRC patients who underwent docetaxel chemotherapy at our center from July 2016 to March 2018 were included in this study. Patients were dichotomized in prostate-specific antigen (PSA) response group (n = 17) versus PSA failure group (n = 15) according to the response to docetaxel. In total 64 matched spectra from 32 mCRPC patients were obtained by using SERS of serum at baseline (q0) and after 1 cycle of docetaxel chemotherapy (q1). Comparing Raman peaks of serum samples at baseline (q0) between two groups, significant differences revealed at the peaks of 638, 810, 890 (p < 0.05) and 1136 cm1 (p < 0.01). The prediction models of peak 1363 cm^-1 and principal component analysis and linear discriminant analysis (PCA–LDA) based on Raman data were established, respectively. The sensitivity and specificity of the prediction models were 71%, 80% and 69%, 78% through the way of leave-one-out cross-validation. According to the results of five-cross-validation, the PCA–LDA model revealed an accuracy of 0.73 and AUC of 0.83.

稀土上转换发光纳米颗粒（UCNPs）可将近红外光转化为紫外可见光，能有效解决光动力抗菌疗法（PACT）中组织穿透深度小、治疗效率低的问题。综述了基于稀土上转换发光纳米平台的光动力抗菌疗法的研究进展，并对新型联合抗菌平台的开发及其在临床上的应用进行了展望。

肿瘤单一药物化疗的效果往往达不到理想的肿瘤治疗效果, 且容易导致耐药。因此, 肿瘤的药物化疗与其他的抗肿瘤治疗方法, 如光热治疗和光动力治疗等, 联合治疗具有明显优势, 并受到越来越多的关注。本工作构建了一种还原性响应的新型智能纳米体系,采用喜树碱聚前药两亲分子(PEG-b-PCPTM)物理包埋光敏剂吲哚箐绿(ICG)。在肿瘤细胞的还原性微环境中, 控制释放化疗药物喜树碱, 激活化疗; 同时, 光敏剂ICG用于光动力治疗, 从而实现化疗与光动力的联合治疗, 表现出良好的抗肿瘤活性。

目的:通过观察高迁移率族蛋白1(HMGB1)、转录因子NF-E2相关因子2(Nrf2)及血红素加氧酶1(HO-1)基因沉默对白血病化疗耐药细胞(K562/A02细胞株)的影响, 探讨该信号通路在白血病化疗耐药中的作用及其可能机制。方法:将HMGB1基因、Nrf2基因及HO-1基因的特异性干扰RNA分别转染阿霉素耐药细胞株K562/A02, 荧光实时定量(RT-PCR)方法检测HMGB1、Nrf2及HO-1的mRNA表达水平, Western blot方法检测HMGB1、Nrf2及HO-1的蛋白表达水平, 免疫荧光方法检测Nrf2的蛋白表达, 并使用CCK-8方法检测转染前后K562/A02细胞株的细胞活性。结果:HMGB1基因、Nrf2基因或HO-1基因沉默的K562/A02细胞活性皆显著低于对照组及空白组(P<0.05), 化疗敏感性恢复。结论:HMGB1高表达导致了白血病细胞株K562/A02对阿霉素的化疗耐药, Nrf2/HO-1信号通路参与了HMGB1诱导的K562/A02细胞的化疗耐药, 其表达上调可恢复K562/A02细胞对阿霉素的敏感性。

探索红外光谱监测肿瘤细胞凋亡的可行性及初步分析。 采用结肠癌细胞系SW620作为诱导细胞模型, MTT法确定最优5-FU诱导浓度, 无血清饥饿培养协同细胞周期阻滞在G1和S期, 傅里叶显微红外光谱仪(FTIR) 联合流式细胞仪(FCM)对SW 620细胞和凋亡的SW 620细胞12 h、 早期凋亡(24 h)和晚期凋亡(48 h)的峰位、 相对峰强等指标进行比较分析。 光谱分析结果显示SW 620对比凋亡细胞有以下特征: (1)与脂类相关谱带1 740 cm-1相对峰强比I1 740/I1 460明显降低(p<0.05), 表明凋亡细胞中脂类相对含量增多。 (2)与氨基酸残基相关谱带1 410 cm-1, I1 460/I1 460在凋亡早期和晚期明显升高(p<0.05), 与丝、 苏氨基酸相关谱带1 120 cm-1 向高波数移动, I1 120/I1 460明显升高(p<0.05), 表明凋亡细胞中DNA双螺旋解链, 氨基酸残基增多。 (3)DNA的反对称伸缩1 240 cm-1向高波数移动, 表明凋亡细胞中核酸分子构象发生改变。 (4)与核酸多糖1 040 cm-1相关谱带在凋亡的24和48 h出现, 向高波数移动, I1 040/I1 460在凋亡晚期降低(p<0.05)。 初步研究结果表明傅里叶变换红外光谱分析可能成为实时无创监测肿瘤化疗的有效方法。