光敏剂纳米粒的功能化修饰及相关生物传感技术研究

Photodynamic therapy (PDT) is a cell-killing process by ligh activation of a photosensitizer in the presence of oxygen, which has rapidly emerged as a promising candidate for the treatment of numerous diseases. The nanomaterials-based biosensor is becoming an entirely new and exciting topic in the field of biomedicine and cancer therapy. At the cutting edge of new PDT developments, many researchers focus on exploring ways to improve the effectiveness of PDT and reduce its side effect. So based on our research achievements on biosensor and PDT, the project aims to develop a novel functional photosensitizer nanoparticles in combination of nanomaterials-assisted biosensing technology to realize the high efficiency and low toxicity of PDT. The photosensitizer nanopartices will be a potential multi-functional candidate including anticancer drug active targeting delivery, stealth, cancer imaging and therapy, and precise PDT dosimetry. The proposed nanomaterials-assisted biosensing technology will be employed to study the dosimetry of the nanoparticles and the diagnosis of cell apoptosis. The physical-chemical characteristics of the nanoparticles including particle size, zeta potential, entrapment efficiency, drug loading, and stability should be also characterized. The cytotoxicity and cancer cell targeting assays of the nanoparticles are performed in order to obtain the effective transporter which can be used in vivo. Antitumor activities for cultured tumor cells and therapeutic mechanism of the nanoparticles by the point of cellular and molecular level will be studied. This study will benefit to the design of biosensing technique, and has remarkable potential in nanomaterials-assisted cancer diagnose and therapy.

光动力疗法（photodynamic therapy, PDT）疗效的提高是恶性肿瘤防治研究中一个迫切希望解决的科学问题。纳米科学的发展推动了生物传感技术在生物医药领域的应用。围绕提高PDT疗效这一中心目标，抓住影响PDT疗效的两个重要因素- - 光敏剂和光动力剂量，基于生物传感技术和PDT研究的工作基础，本项目创新性地将纳米增效的新型生物传感技术与光敏剂纳米粒的功能化修饰设计有机结合，将分子识别与生物传感技术相互渗透融合，制备集主动靶向药物传输、肿瘤分子成像与治疗、光动力剂量检测等功能为一体的光敏剂纳米粒。并通过检测该纳米粒的物理化学特性、安全性和靶向性，筛选出理想的具有分子识别功能的纳米粒，利用所构建的纳米增效生物传感界面研究纳米粒抑瘤效应，并结合抗肿瘤活性实验判断疗效控制剂量，发挥光敏剂高效低毒优势，实现提高PDT疗效的研究目标。本项目将为恶性肿瘤的诊断和治疗提供新思路和新技术。

癌症是世界范围内最具破坏性的疾病之一，严重威胁人类的生命和健康。肿瘤光动力治疗是近年肿瘤学科和生物医学研究的热点。光动力疗法疗效的提高是恶性肿瘤防治研究中一个迫切希望解决的科学问题。围绕提高光动力疗法疗效这一中心目标，本项目光敏剂纳米粒的功能化修饰及相关生物传感技术研究结合纳米技术、生物医学工程、化学生物学和肿瘤分子生物学等学科交叉技术，制备新型的高效光敏剂纳米粒新剂型。以壳聚糖、磷脂化的聚乙二醇以及纳米碳管等为光敏剂的运输载体，并利用共价修饰方法将肿瘤靶向分子叶酸和RGD偶联在纳米粒表面，进一步利用化学固定和物理包埋方法获得负载光敏剂的纳米粒药物新剂型，同时构建了基于纳米金，纳米金棒和石墨烯的生物传感活性界面。对光敏剂纳米粒粒径、包封率、载药量、稳定性以及光敏剂纳米粒的活性氧产生等情况进行了相关的表征。利用细胞靶向性实验和在体靶向实验评估了纳米粒的靶向效果，并利用细胞毒性和在体毒性实验并结合所构建的纳米增效生物传感界面研究了纳米粒抑瘤效应。通过优化实验条件，完善研究方法，进一步用于上转换光敏剂纳米粒和磁性光敏剂纳米粒的构建。所构建的光敏剂纳米粒通过受体介导的主动靶向和EPR效应被动靶向聚集到肿瘤部位，减少了组织的非特异性吸附，具有良好的靶向性。光敏剂纳米粒在特定波长激光的照射下，可有效杀死肿瘤细胞并表现出较低的细胞暗毒性。本研究在提高肿瘤治疗效果的同时降低了系统的毒副作用，实现了提高光动力疗法疗效这一中心目标，将为恶性肿瘤的诊断和治疗提供新思路和新技术。