靶向光敏剂NaYF4:Yb,Tm@ NaGdF4:Yb@TiO2@PEI-PAA-FA的制备和性能

采用水解法用TiO_2包覆上转换纳米粒子Na YF4:Yb,Tm@NaGdF4:Yb,然后修饰聚乙烯亚胺(PEI)和聚丙烯酸(PAA)并偶联叶酸(FA),制备了叶酸受体靶向纳米光敏剂(NaYF4∶Yb,Tm@NaGdF4∶Yb@TiO_2@PEIPAA-FA)。借助XRD和TEM表征NaYF4∶Yb,Tm@NaGdF4∶Yb@TiO_2的物相和形貌,FTIR和Zeta电位证实有机成分的成功修饰,并测试了产物的上转换发光光谱。结果表明:在980 nm近红外光(NIR)下,纳米光敏剂存在下的1,3-二苯基异苯并呋喃溶液吸收光谱的降低证明了单线态氧的产生。此外,纳米光敏剂可以载带阿霉素(DOX),最大载药率为50.8%,包封率为84.7%。载药后的纳米光敏剂中DOX释放对介质具有pH响应性,在NIR照射的酸性介质(pH=5.0)中12 h的累积缓释率为38.1%,远高于中性介质(pH=7.4)的10.4%。     

术前新辅助化疗对宫颈癌患者临床疗效的观察

目的探讨宫颈癌患者术前新辅助静脉化疗的临床疗效。方法收集本院2006年1月至2008年1月收入院的35例宫颈癌(Ⅰb-Ⅱa)患者,术前给以BIP方案(顺铂+异环磷酰胺+博来霉素)的新辅助静脉化疗,所有病人均完成2个疗程化疗,化疗结束后14d经妇科检查,B超测量宫颈肿块消退情况,按UICC疗效标准评价疗效。化疗结束后3周行子宫广泛切除加盆腔淋巴结清扫。结果化疗有效率CR34.3%(12/35),PR45.7%(16/35),SD20.0%(7/35),PD0%(0/35),其中Ⅰb1期有效率100(7/7),Ⅰb2期有效率90.47%(19/21),Ⅱa期有效率57.1%(4/7)。宫颈肿块<4cm有效化疗有效率CR34.3%(12/35),率92.9%(13/14),≥4cm有效率71.4%(15/21);术后病理提示阴道切缘、宫旁浸润及盆腔淋巴结转移均阴性。结论新辅助静脉化疗作为早期宫颈癌术前治疗,可以明显缩小和消退宫颈肿块,减少术后宫旁浸润、淋巴结转移,降低术后并发症、减少术后复发。     

Oxidatively activated DNA-modifying agents for selective cytotoxicity

DNA‐modifying agents are stalwarts of chemotherapeutic cancer treatments, but require significant design improvements to improve selectivity, minimize side effects, and for their widespread use to continue. Herein we present a novel design strategy in which DNA‐modifying agents contain an oxidizable leaving group and a nitrogen mustard. The agents form strong electrophiles specifically when oxidized. Activation, measured by hydrolysis, illustrates that oxidants increase reactivity 1700‐fold. Reaction in the presence of 2′‐deoxyguanosine leads to the formation of lesions. Cytotoxicity measured in HeLa cells showed that low IC₅₀ values require an oxidizable hydroquinone and a nitrogen mustard fragment. Cytotoxicity measurements in 15 cancer cell lines demonstrates that oxidatively activated DNA‐modifying agents are highly selective, as the analogue tested has IC₅₀ values less than 10 μM for only three of the 15 cell lines; in contrast, cisplatin is highly toxic to 13 of the 15 cell lines. The selective cytotoxicity of oxidatively activated DNA‐damaging agents could be useful against kidney cancer cells, as the 786‐O cell line model assay resulted in an IC₅₀ value of 5 μM .     

The application of carbon nanotubes in target drug delivery systems for cancer therapies

Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.     

ERCC1对胃癌患者手术及化疗后生存预测的意义

Objective:The aim of this study was to evaluate the effect of the excision repair cross-complementing (ERCC1) expression on survival in advanced gastric cancer patients who underwent surgical resection and treated with oxaliplatin-based adjuvant chemotherapy. Methods: Sixty-three patients who underwent surgical resection for cure and treated with oxaliplatin-based adjuvant chemotherapy were included in this study. The expressions of ERCC1 of gastric cancer were examined by immunohistochemistry and the patients were categorized into ERCC1-(+) and ERCC1-(-) groups. The relation between ERCC1 expression and survival of patients was examined. Results: Of the 63 eligible patients, 36 patients (57.1%) had tumor with a positive expression of ERCC1 and the remaining 27 patients had tumor with a negative ERCC1 expression. Expression differences of ERCC1 didn't correlated with age (P - 0.827), gender (P = 0.12), differentiation (P = 0.113), historical type (P = 0.942), site of tumor (P = 0.221), size of tumor (P = 0.608), stage (P = 0.815) and lymphatic invasion (P = 0.165). Overall survival (OS) was significantly longer in patients without ERCC1 expression, when compared to patients with ERCC1 expression (P = 0.023). Multivariate analysis revealed that ERCC1 expression significantly impacted on OS (MR: 4.049; P = 0.000). Conclusion: We concluded that resected and treated with oxaliplatin-based adjuvant chemotherapy gastric cancer patients without ERCC1 expression have a better survival when compared to patients with ERCC1 expression. ERCC1 expression will hopefully provide a rational basis for improving adjuvant chemotherapeutic strategies for gastric cancer patients. ERCC1, itself, may be a prognostic factor for gastric cancer.     

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。     

Biocompatible,Uniform, and Redispersible Mesoporous Silica Nanoparticles for Cancer‐Targeted Drug Delivery In Vivo

Engineering multifunctional nanocarriers for targeted drug delivery shows promising potentials to revolutionize the cancer chemotherapy. Simple methods to optimize physicochemical characteristics and surface composition of the drug nanocarriers need to be developed in order to tackle major challenges for smooth translation of suitable nanocarriers to clinical applications. Here, rational development and utilization of multifunctional mesoporous silica nanoparticles (MSNPs) for targeting MDA‐MB‐231 xenograft model breast cancer in vivo are reported. Uniform and redispersible poly(ethylene glycol)‐incorporated MSNPs with three different sizes (48, 72, 100 nm) are synthesized. They are then functionalized with amino‐β‐cyclodextrin bridged by cleavable disulfide bonds, where amino‐β‐cyclodextrin blocks drugs inside the mesopores. The incorporation of active folate targeting ligand onto 48 nm of multifunctional MSNPs (PEG‐MSNPs48‐CD‐PEG‐FA) leads to improved and selective uptake of the nanoparticles into tumor. Targeted drug delivery capability of PEG‐MSNPs48‐CD‐PEG‐FA is demonstrated by significant inhibition of the tumor growth in mice treated with doxorubicin‐loaded nanoparticles, where doxorubicin is released triggered by intracellular acidic pH and glutathione. Doxorubicin‐loaded PEG‐MSNPs48‐CD‐PEG‐FA exhibits better in vivo therapeutic efficacy as compared with free doxorubicin and non‐targeted nanoparticles. Current study presents successful utilization of multifunctional MSNP‐based drug nanocarriers for targeted cancer therapy in vivo.     

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.     

Gold Nanoframeworks with Mesopores for Raman–Photoacoustic Imaging and Photo‐Chemo Tumor Therapy in the Second Near‐Infrared Biowindow

Gold‐based nanostructures with tunable wavelength of localized surface plasmon resonance (LSPR) in the second near‐infrared (NIR‐II) biowindow receive increasing attention in phototheranostics. In view of limited progress on NIR‐II gold nanostructures, a particular liposome template‐guided route is explored to synthesize novel gold nanoframeworks (AuNFs) with large mesopores (≈40 nm) for multimodal imaging along with therapeutic robustness. The synthesized AuNFs exhibit strong absorbance in NIR‐II region, affording their capacity of NIR‐II photothermal therapy (PTT) and photoacoustic (PA) imaging for deep tumors. Functionalization of AuNFs with hyaluronic acid (HA) endows the targeting capacity for CD44‐overexpressed tumor cells while gatekeeping doxorubicin (DOX) loaded into mesopores. Conjugation of Raman reporter 4‐aminothiophenol (4‐ATP) onto AuNFs yields a surface‐enhanced Raman scattering (SERS) fingerprint for Raman spectroscopy/imaging. In vivo evaluation of HA‐4‐ATP‐AuNFs‐DOX on tumor‐bearing xenografts demonstrates its high efficacy in eradication of solid tumors in NIR‐II under PA–Raman dual image‐guided photo‐chemotherapy. Thus, current AuNFs offer versatile capabilities for phototheranostics.     

98例局部晚期乳腺癌介入化疗并发症的临床分析

目的：分析局部晚期乳腺癌介入化疗的主要并发症,探讨其原因和防治措施。方法：局部晚期乳腺癌98例,在DSA室于局麻下经尺动脉或股动脉穿刺插管,将导管尖端送至锁骨下动脉与胸廓内动脉开口交界处近端并固定,经导管灌注化疗药物。结果：20例发生了较明显的并发症,其中患侧上肢、肩背部疼痛11例,局部皮肤损伤6例,上肢肌肉萎缩1例,穿刺部位出血2例。结论：出现上述并发症的原因可能与介入途径、留管时间、化疗疗程、化疗药物种类、用量、浓度、推药速度及推注药物时操作不当等因素有关。