Cancer Cell Membrane-Coated Nanosuspensions for Enhanced Chemotherapeutic Treatment of Glioma

Effective intracerebral delivery is key for glioma treatment. However, the drug delivery system within the brain is largely limited by its own adverse physical and chemical properties, low targeting efficiency, the blood–brain barrier and the blood–brain tumor barrier. Herein, we developed a simple, safe and efficient biomimetic nanosuspension. The C6 cell membrane (CCM) was utilized to camouflaged the 10-hydroxycamptothecin nanosuspension (HCPT-NS) in order to obtain HCPT-NS/CCM. Through the use of immune escape and homotypic binding of the cancer cell membrane, HCPT-NS/CCM was able to penetrate the blood–brain barrier and target tumors. The HCPT-NS is only comprised of drugs, as well as a small amount of stabilizers that are characterized by a simple preparation method and high drug loading. Similarly, the HCPT-NS/CCM is able to achieve targeted treatment of glioma without any ligand modification, which leads it to be stable and efficient. Cellular uptake and in vivo imaging experiments demonstrated that HCPT-NS/CCM is able to effectively cross the blood–brain barrier and was concentrated at the glioma site due to the natural homing pathway. Our results reveal that the glioma cancer cell membrane is able to promote drug transport into the brain and enter the tumor via a homologous targeting mechanism.     

Advances in Biomimetic Nanoparticles for Targeted Cancer Therapy and Diagnosis

Biomimetic nanoparticles have recently emerged as a novel drug delivery platform to improve drug biocompatibility and specificity at the desired disease site, especially the tumour microenvironment. Conventional nanoparticles often encounter rapid clearance by the immune system and have poor drug-targeting effects. The rapid development of nanotechnology provides an opportunity to integrate different types of biomaterials onto the surface of nanoparticles, which enables them to mimic the natural biological features and functions of the cells. This mimicry strategy favours the escape of biomimetic nanoparticles from clearance by the immune system and reduces potential toxic side effects. Despite the rapid development in this field, not much has progressed to the clinical stage. Thus, there is an urgent need to develop biomimetic-based nanomedicine to produce a highly specific and effective drug delivery system, especially for malignant tumours, which can be used for clinical purposes. Here, the recent developments for various types of biomimetic nanoparticles are discussed, along with their applications for cancer imaging and treatments.     

靶向性多肽修饰荧光功能化碳纳米管的制备及靶向肿瘤细胞的初步研究

以羟基化多壁碳纳米管(MWNT-OH)为引发剂,通过原位负离子开环聚合制备了生物相容性多羟基超支化聚缩水甘油接枝的碳纳米管(MWNT-HPG),利用酯化反应将荧光分子罗丹明6B标记于聚合物上,然后聚合物上的羟基和丁二酸酐反应将其转化为羧基.用TGA、FTIR、TEM、SEM等手段对产物进行了表征.用靶向表皮生长因子受体(EGFR)的小分子多肽D4修饰了所得的荧光功能化碳纳米管,并将其做为受体介导靶向肿瘤细胞的纳米载体,通过噻唑蓝(MTT)比色法评价功能化碳纳米管作为载体的安全性.用荧光显微镜观察其与人肺腺癌细胞SPCAI细胞的结合状态.结果证明了其有希望成为受体介导靶向肿瘤系统的纳米载体.     

两亲嵌段共聚物胶束用作医用材料

两亲嵌段共聚物可以在水溶液中自组装形成亲水性链段为外壳、疏水性链段为内核的胶束,这种胶束能够用作药物载体而引起人们极大的关注。本文综述了两亲嵌段共聚物胶束用作医用材料的研究进展,主要内容包括医用两亲嵌段共聚物的种类,胶束化,以及用作诊断试剂载体、药物缓释载体、靶向载体等。两亲嵌段共聚物胶束用作磁共振造影剂载体有利于肿瘤的诊断,用作药物缓释载体可以有效增溶难溶性抗肿瘤药物,延长药物在体内的血液循环时间。此外,通过对胶束表面进行修饰或者施加外场,还可以实现靶向功能。因此,两亲嵌段共聚物胶束在医用材料领域有着广阔的发展前景。     

促性腺激素释放激素类似物-紫杉醇靶向抗肿瘤缀合物的合成及评价

以促性腺激素释放激素类似物(GnRHa)为靶向配体, 以紫杉醇为抗癌因子, 分别以硫醚键和二硫键为连接臂, 设计合成了2个靶向抗肿瘤缀合物. 研究了缀合物的肿瘤细胞增殖抑制活性和GnRH受体结合活性, 结果表明, 2个缀合物均具有较强的抗肿瘤活性和GnRH受体亲和力; 另外, 血浆稳定性实验结果显示, 以硫醚键偶联的缀合物1在血浆中孵育24 h, 原型保留仍在50%以上, 具有较高的稳定性.     

基于环糊精的靶向药物传递系统

癌症等恶性增殖疾病的靶向治疗有赖于靶向药物传递系统（targeted drug delivery system,TDDS）的开发。环糊精具有低毒、易修饰等优良性质,并可通过与药物分子形成包合物而提高药物的溶解性、稳定性、安全性和生物利用度等,因而具有成为优秀药物载体的潜力。环糊精不仅可以以其本身或修饰环糊精的形式充当载体,还可通过聚轮烷、阳离子聚合物或纳米粒等形式构建有效的药物载体。肿瘤或人体某些病变部位的细胞表面存在过度表达的生物受体如叶酸受体、去唾液酸糖蛋白受体、透明质酸受体、转铁蛋白受体和整合素受体等,可以与其相应的配体产生特异性识别。用适当的化学方法将配体分子如叶酸、单糖或寡糖、透明质酸、转铁蛋白及RGD肽等键接在基于环糊精的载体上,可形成具有靶向性质的药物载体,进而与药物分子一起构筑靶向药物传递系统。这种药物传递系统不仅针对于化学治疗药物,在核酸传递中也得到了丰富的应用。本文综述了基于环糊精的靶向药物传递系统的靶向机理及最新研究进展,并对其发展前景作了展望。     

含乳糖聚电解质靶向微胶囊的层层自组装构筑

设计合成了己二酸乳糖乙烯酯/对苯乙烯磺酸钠共聚物（PLESS）,通过层层自组装技术构筑聚烯丙基胺盐酸盐（PAH）与含乳糖聚电解质PLESS的靶向微胶囊。以紫外-可见吸收光谱监测了PAH与PLESS在平面的石英片进行层层自组装过程,研究了不同实验条件（聚电解质浓度、溶液盐度、盐种类）对PAH/PLESS多层膜自组装的影响;PAH与PLESS在球形碳酸钙微球模板上层层自组装,去除模板后得到层状结构的微胶囊,用透射电镜（TEM）等方法观察其形态形貌;通过花生凝集素识别考察其潜在靶向性;通过细胞MTT活性试验评价其生物相容性。     

OXIRIS project: Development of a new XRF device for the simultaneous detection and treatment of cancer

A novel and suitable energy-dispersive X-ray fluorescent (EDXRF) device, currently at the prototype stage, the Project OXIRIS (Orthovoltage X-Ray–Induced Radiation System), is presented for the simultaneous detection and treatment of cancer diseases. Monte Carlo simulation and experimental results of EDXRF signals from a small deep artificial tumor consisting of a solution of gold nanoparticles bio-targeted and immersed in a tissue-bioequivalent matrix are presented and compared. Briefly, the device consists of a dynamic orthovoltage X-ray fluence concentration coupled to confocal with an EDXRF system along with a sample holder for 3D scanning; all integrated and controlled by a dedicated software capable of controlling the whole operation functionalities: the X-ray source, the rotating arm, the sample holder, and the detection system. The software also includes dedicated subroutines for X-ray fluorescent spectra processing to correlate K-lines signal at each acquisition position with the corresponding high atomic number elements' concentration to produce a 3D distribution according to the user-defined grid. The confocal configuration ensures that the detected signal comes exclusively from the excited volume as defined by the bulk of the focal spot. Hence, the 3D image is achieved by scanning the sample holder through the movement of the sample-carrier stretcher moved by step motors in the 3 coordinated axes. The feasibility of the proposed methodology and the design of the prototype have been successfully demonstrated experimentally, targeting gold nanoparticles in water-equivalent phantoms.     

Site-specific conjugation of ScFvs antibodies to nanoparticles by bioorthogonal strain-promoted alkyne-nitrone cycloaddition

Particularly suitable: An N-terminal serine mutant of anti-HER2 scFv antibody was conjugated to polymer-coated magnetofluorescent nanoparticles by strain-promoted alkyne-nitrone cycloaddition. The resulting nanoparticles (see scheme) proved effective in targeting and labeling HER2-positive breast cancer cells.