A Novel Multifunctional Bionanoprobe-Based Phototherapy for Metastatic Cancers

描述(申请人提供)：激光和纳米材料是20世纪最重要的两项技术进步。激光和纳米技术的结合在生物和医学领域有着巨大的希望。该项目的长期目标是开发一种多功能的生物探针，用于靶向药物输送、肿瘤成像和转移性癌症的光免疫治疗。PI计划使用一种新的方法(正在申请专利)来构建稳定的单壁碳纳米管(SWNT)溶液，使用高效免疫刺激剂糖化壳聚糖(GC)作为有效的表面活性剂。在这个项目中，PI计划构建、模拟和校准这种生物探针，确定它的物理和生物学特性，研究它与正常和肿瘤的相互作用 细胞，研究其毒性，并确定其在体外和体内治疗转移性肿瘤的光免疫效果。我们假设这种生物探针可以携带不同的分子进入肿瘤细胞。我们进一步假设，当这种新型的生物探针定位在肿瘤细胞内并结合适当波长的激光照射时，可以诱导时间和空间同步的光热和免疫反应来治疗转移性癌症。这种生物阳离子探针的新奇之处在于其独特的分子结构--SWNT和GC，因此可以在稳定的纳米管溶液中形成较强的非共价键。此外，利用在近红外区有吸收峰的原位SWNT-GC可以实现选择性光热相互作用。这确保了在非侵入性激光照射期间目标组织的空间和时间热生物效应同步。在这个项目中，PI将用荧光分子修饰BionanoProbe，以研究其细胞分布，并探索其携带不同多肽和治疗剂进入肿瘤细胞的能力。PI还将使用磁共振测温技术来确定激光照射期间目标肿瘤组织中的实时三维温度分布，这可能有助于建立肿瘤组织温度上升与诱导的免疫反应之间的关联。具体地说，PI计划实现以下目标：(1)构建、校准、模拟、调查和修改多功能BionanoProbe；(2)研究多功能BionanoProbe的细胞效应；以及(3)确定激光-SWNT-GC治疗转移性癌症的体内疗效。该项目的成功完成将为未来探索这种新型多功能生物探针在生物学和医学，特别是在癌症治疗中的潜在应用铺平道路。

DESCRIPTION (provided by applicant): Lasers and nanomaterials are two of the most significant technological advances of the 20th century. The combination of lasers and nanotechnology holds great promise in the fields of biology and medicine. The long- term objective of this project is to develop a multifunctional bionanoprobe for targeted drug delivery, tumor imaging, and photoimmunotherapy for metastatic cancers. The PIs plan to use a novel method (patent pending) to construct a stable solution of single-walled carbon nanotube (SWNT) using a highly potent immunostimulant, glycated chitosan (GC), as an effective surfactant. In this project, the PIs plan to construct, simulate, and calibrate this bionanoprobe, determine its physical and biological characteristics, study its interactions with normal and tumor cells, investigate its toxicity, and determine its photoimmunological effects for treatment of metastatic tumors both in vitro and in vivo. We assume that this bionanoprobe can carry different molecules into tumor cells. We further hypothesize that this novel bionanoprobe, when localized inside tumor cells and combined with laser irradiation of appropriate wavelengths, can induce temporally and spatially synchronized photothermal and immunological reactions for treatment of metastatic cancers. The novelty of this bionanoprobe lies in the unique molecular structures of SWNT and GC so that a strong non- covalent bond can be formed for a stable nanotube solution. Furthermore, selective photothermal interaction can be achieved using in situ SWNT-GC with an absorption peak in the near-infrared region. This ensures a synchronized spatial and temporal thermo-biological effect in target tissue during non-invasive laser irradiation. In this project, the PIs will modify the bionanoprobe with fluorescent molecules to study its cellular distribution and to explore its capability to carry different peptides and therapeutic agents into tumor cells. The PIs will also use magnetic resonance thermometry to determine real-time, 3-dimensional temperature distributions in target tumor tissue during laser irradiation, which could help establish a correlation between temperature increases in tumor tissue and induced immunological responses. Specifically, the PIs plan to achieve the following aims: (1) To construct, calibrate, simulate, investigate, and modify the multifunctional bionanoprobe; (2) To investigate the cellular effects of the multifunctional bionanoprobe; and (3) To determine in vivo efficacy of laser-SWNT-GC for treatment of metastatic cancers. Successful completion of this project will pave the way to future explore the potential applications of this novel multifunctional bionanoprobe in biology and medicine, particularly in cancer treatment.