金纳米棒介导的温和热疗对乳腺癌干细胞的致敏作用和肿瘤干细胞靶向性多功能纳米药物设计

In recent years, more and more researches manifest that cancer stem cells play a key role in the initiation, development and metastasis of tumors. Cancer stem cells are highly resistant to current chemotherapy and radiotherapy. Therefore, elimination of this cell subpopulation is critical for the successful cancer treatment. Gold nanorods (AuNRs) are novel metal nanomaterials which have been widely developed for photothermal cancer therapy and imaging. Our previous study found that cancer stem cells were more sensitive to AuNRs mediated photothermal therapy than non cancer stem cells. Meanwhile, AuNRs mediated mild hyperthermia could sensitize the multidrug resistant breast cancer cells to chemotherapy. On the basis of previous work, the present project intends to address the following questions: 1) Sensitization of breast cancer stem cells to chemotherapy by AuNRs mediated mild hyperthermia; 2) The regulation of AuNRs mediated hyperthermia on the metabolic pathways closely related to multidrug resistance of cancer stem cells; 3) Design of AuNRs drug carriers which can efficiently target cancer stem cells; 4) Delivery of cancer stem cells inhibitors by AuNRs to achieve multifunctional theranostics by combining light triggered drug release, hyperthermia, targeting and imaging.

越来越多的证据表明，肿瘤干细胞在肿瘤的发生、发展和转移过程中发挥关键作用。肿瘤干细胞对传统的化疗和放疗都具有高度的耐受性，因此，消除这一类细胞是成功治疗肿瘤的关键。 金纳米棒（AuNRs）是一种新型贵金属纳米材料，在肿瘤光热治疗和成像方面有着广泛应用。我们前期的研究发现，肿瘤干细胞对AuNRs介导的光热治疗比普通肿瘤细胞具有更高的敏感性。同时，AuNRs介导的温和热疗能够致敏乳腺癌耐药细胞，使其化疗敏感性显著增加。在前期工作的基础上，本项目拟解决以下问题：1）AuNRs介导的温和热疗对乳腺癌干细胞化疗的增敏作用；2）AuNRs介导的温和热疗对乳腺癌干细胞高度耐药性密切相关的细胞代谢通路的调节；3）设计靶向肿瘤干细胞的AuNRs药物载体，并进行细胞水平和动物水平的成像；4）以AuNRs载带肿瘤干细胞抑制剂，通过激光控制的药物释放实现靶向、化疗、热疗和成像的多功能诊疗一体化。

金纳米棒（AuNRs）是一种重要的贵金属纳米材料，在肿瘤光热治疗和医学成像领域有着广泛应用。本项目针对包括AuNRs在内的多种金属纳米材料进行了广泛研究，包括纳米医学领域中药物载带、医学成像、靶向肿瘤干细胞及相关治疗应用中的生物学机制问题。这些研究探索大大丰富了纳米医学中针对乳腺癌在内的实体瘤的诊断与治疗方法学，并在动物水平上实现了肿瘤干细胞的抑制与消除，降低肿瘤的复发与转移。这一系列研究成果为进一步肿瘤治疗、诊断应用提供了借鉴，并具有一定的转化应用潜力。