癌症因其复杂性和致命性而受到人们的广泛关注。到目前为止，已有许多针对肿瘤的治疗方法，如放疗、化疗、免疫治疗、基因治疗等。这些治疗策略在抑制肿瘤增殖方面产生了显著效果，但仍有很大的改进空间。例如传统癌症治疗中使用的大多数药物缺乏靶向特异性以及强亲和力，导致治疗效果有限，对正常组织毒性较高。光动力治疗（PDT）作为一种新兴的肿瘤治疗方法，对局部肿瘤具有高选择性和有效性，是一种有前途的非侵入性治疗方法。通常其治疗效果依赖于PDT光敏剂在光照射下产生活性氧（ROS）的能力。然而，目前用于临床的商用PDT光敏剂的激发波长主要位于可见光区域，导致组织穿透力受限和较弱的光毒性。针对以上问题，本文设计合成了一种基于氮杂氟硼吡咯（Aza-BODIPY）结构的光敏剂，通过化学修饰拓展其共轭体系、提高光敏剂的光动力治疗效果。利用纳米共沉淀技术制备了具有良好水分散性的纳米颗粒（Nanoparticles，NPs），并对其光动力治疗的能力进行了初步研究。

内源性次氯酸（HOCl）是由过氧化氢（H₂O₂）和氯离子（Cl^-）在髓过氧化物酶的催化下形成的。HOCl作为一种活性氧，具有杀死多种病原体的重要功能。然而，过量的HOCl会导致一些疾病，如关节炎、肾病和癌症。因此，HOCl成像技术的发展对我们了解HOCl在生物学中的作用非常重要。本文就之前设计合成的一种水溶性的具有AIE活性的荧光有机纳米粒子用于HOCl的检测和细胞成像研究。

本论文的主要内容如下：

1. 基于肿瘤的弱酸性微环境，通过将吡啶基修饰到Aza-BODIPY母核上，设计并合成了一个具有近红外吸收的pH敏感光敏剂Py-BDP。吡啶基团可作为质子受体在酸性环境中结合氢离子，增强激发态Py-BDP的系间窜越，进一步提高光敏剂产生活性氧的能力。与Pluronic F127嵌段聚合物所制备的纳米粒子Py-BDP NPs的紫外吸收值进一步红移。共聚焦成像以及细胞毒性实验结果表明，Py-BDP NPs在肿瘤细胞与正常细胞中产生单线态氧的能力有显著差别，同时表现出较低的暗毒性，因此具有成为肿瘤特异性光敏剂的潜力。

2. 聚集诱导发光（AIE）材料，因其低本底、高信噪比、高量子产率、良好的稳定性等优点而受广泛关注。本课题组设计并合成了一个两亲性荧光有机纳米粒子THG-1。THG-1由三部分组成，四苯乙烯为荧光团，乳糖基团为助溶基团，酰腙基团为连接基团，且可作为HOCl的反应识别位点。通过乳糖修饰后的两亲性分子THG-1可自组装为大小均一的纳米颗粒，在之前的工作中被证实可对HOCl进行高选择性和高灵敏检测。THG-1与HOCl作用后的形态也产生了较显著变化，THG-1表现出较低的细胞毒性和良好的光稳定性，被成功应用于活细胞外源性和内源性HOCl的成像。

Cancer has attracted extensive attention due to its complexity and lethality. So far, many methods have been proposed for tumor imaging and therapy, including chemotherapy, radiotherapy, immunotherapy, gene therapy and so on. These therapeutic strategies have shown significant effects in increasing cytotoxicity of tumor cells and inhibiting tumor proliferation. At present, these therapies still have a lot of room for improvement. For example, most of the traditional drugs used in cancer treatment lack of specific affinity, limited therapeutic effect and high toxicity in normal tissues. Photodynamic therapy (PDT) is an emerging tumor treatment method, which is a very promising noninvasive treatment method due to its high selectivity and effectivity for local tumors. Generally, the therapeutic effect depends on the ability of PDT photosensitizer to produce reactive oxygen species (ROS) under light irradiation. Based on the above problems, a photosensitizer with Aza-BODIPY structure as the core was designed and synthesized in this paper. The conjugated system was extended by chemical modification to improve the photodynamic therapy effect of photosensitizers. Nanoparticles (NPs) with good water dispersion were prepared by nanoprecipitation, and their ability to produce reactive oxygen species (ROS) was studied. Endogenous hypochlorite (HOCl) is formed from hydrogen peroxide (H₂O₂) and chloride ion (Cl^-) by the catalysis of enzyme myeloperoxidase. As a kind of reactive oxygen species, HOCl plays an important role in killing many pathogens. However, excessive HOCl can lead to some diseases, such as arthritis, kidney disease and cancer. Therefore, the development of fluorescence imaging technology of HOCl is crucial for us to understand its role in biology. A kind of water-soluble fluorescent organic nanoparticles with AIE activity were designed and synthesized for the detection of HOCl and cell imaging.The specific contents of this paper are as follows:

1.       Based on the weak acidic microenvironment of tumor, a photosensitizer Py-BDP with near infrared absorption was designed and synthesized by modifying the pyridine group on the Aza-BODIPY structure. Pyridine group can be used as a proton acceptor to bind hydrogen ions in acidic environment, which can enhance the intersystem crossing of excited Py-BDP and further improve the ability of photosensitizer to produce reactive oxygen species. The UV absorption value of the NPs prepared with copolymer pluronic F-127 was further red shifted. Confocal imaging experiments showed that the ability of Py-BDP NPs to produce singlet oxygen in tumor cells was higher than that in normal cells. At the same time, the low dark toxicity of Py-BDP NPs further proves that Py-BDP has the potential to become a tumor specific photosensitizer.

2.       Aggregation-induced emission (AIE) materials have attracted much attention due to their low background, high signal-to-noise ratio, high quantum yield and good stability. Therefore, our group designed and synthesized an amphiphilic fluorescent organic nanoparticle THG-1. THG-1 is composed of three parts, tetraphenylethylene as fluorophore, lactose group as solubilizing group, hydrazone group as connecting group, and can be used as the reaction recognition site of HOCl. The amphiphilic molecule THG-1 modified by lactose can self assemble into nanoparticles with uniform size, which has been proved to be highly selective and sensitive for the detection of HOCl in previous work. THG-1 showed low cytotoxicity and good photostability. What's more, THG-1 has been successfully applied to imaging exogenous and endogenous HOCl in living cells.