Enzyme-Triggerable Stealth Release (ETSR) of targeted nanoparticles for cancer gene therapy

用于癌症基因治疗的靶向纳米粒子的酶触发隐形释放（ETSR）

基本信息

批准号：
EP/F003188/1
负责人：
Maya Thanou
金额：
$ 49.38万
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2007
资助国家：
英国
起止时间：
2007 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=EP%2FF003188%2F1
关键词：
Enzyme Triggerable Stealth Release ETSR

项目摘要

Targeted drug delivery to disease tissues like tumours is the ultimate therapeutic strategy. If drugs can accumulate in tumour tissue, then unwanted side effects including cellular toxicity can be avoided and therapeutic effects may be improved since both dose and efficacy can increase. In this project our main aim is to harness the potential of nanomedicine by preparing self-assembly, synthetic nanoparticles that carry drugs inside but have and a polymer coating on the outside. However, while the polymer coating is excellent in helping to improve blood-circulation times, local release of encapsulated drugs in or near tumour target cells is heavily impaired. This problem should be soluble by ensuring that the polymer can be released at the required time inside the tumour itself bringing cell death exclusively to tumour cells. Our specific approach is to introduce polymers with peptide sequences that are also substrates for tumour specific enzymes. When such peptide modified nanoparticles reach tumours, those enzymes present should then strip-off the polymer coating revealing core nanoparticles that can easily enter cells and deliver encapsulated drug(s) to local tumour cells. We will construct these nanoparticles by preparing all necessary building blocks chemically and assemble these in such way that peptide sequences will be readily available for the tumour specific enzyme(s). Nucleic acids will used as the first drugs since these can be very specific and are arguably safer than the anticancer cytotoxic agents.

将药物靶向递送至肿瘤等疾病组织是最终的治疗策略。如果药物可以在肿瘤组织中积聚，则可以避免包括细胞毒性在内的不良副作用，并且可以提高治疗效果，因为剂量和功效都可以增加。在这个项目中，我们的主要目标是通过制备自组装的合成纳米颗粒来利用纳米医学的潜力，这些纳米颗粒内部携带药物，但外部有聚合物涂层。然而，虽然聚合物涂层在帮助改善血液循环时间方面表现出色，但肿瘤靶细胞内或附近的封装药物的局部释放受到严重损害。通过确保聚合物可以在肿瘤内部所需的时间释放，仅导致肿瘤细胞死亡，这个问题应该可以得到解决。我们的具体方法是引入具有肽序列的聚合物，这些肽序列也是肿瘤特异性酶的底物。当这种肽修饰的纳米颗粒到达肿瘤时，存在的那些酶应该剥离聚合物涂层，露出核心纳米颗粒，该纳米颗粒可以轻松进入细胞并将封装的药物递送至局部肿瘤细胞。我们将通过化学方法制备所有必要的构建块来构建这些纳米颗粒，并以这样的方式组装它们，使得肽序列可以容易地用于肿瘤特异性酶。核酸将作为第一种药物，因为它们具有非常特异性，并且可以说比抗癌细胞毒性药物更安全。