【作者】 李超；

【导师】 杨红；

【作者基本信息】 上海师范大学 ， 无机化学， 2023， 硕士

【摘要】 根据Warburg效应,肿瘤细胞生长需要氧气和大量的营养物质。除此之外,肿瘤相关巨噬细胞（TAMs）是在各种癌症模型的肿瘤微环境（The tumor microenvironment,TME）中发现的主要免疫细胞类型,对于生长中的肿瘤,发现M2表型的巨噬细胞会促进肿瘤细胞的生长和侵袭,触发血管生成,同时降低T细胞活性。因此,开发对抑制肿瘤细胞能量代谢和诱导巨噬细胞极化的纳米系统对于肿瘤治疗非常有意义。基于此,我们设计了一种生成活性氧（ROS）的纳米平台（MnClPc-HSA@GOx）。在超声、冰浴的条件下,我们通过人血清蛋白（HAS）包裹锰酞菁配合物（MnClPc）,并将葡萄糖氧化酶（GOx）负载到MnClPc@HSA纳米粒子上。这种以HSA为主要成分的纳米平台,利用GOx催化分解葡萄糖产生过氧化氢和葡萄糖酸,并通过MnClPc的作用,将H₂O₂催化为ROS。实验表明,这种纳米平台,一方面,阻断了肿瘤细胞的葡萄糖供应,抑制了肿瘤细胞的能量代谢;另一方面,产生的ROS介导TAMs的极化,将M2型（抗炎型）逆转为M1型（促炎型）。最终,实现了良好的肿瘤抑制效果。更多还原

【Abstract】 According to the Warburg effect,tumor cells need oxygen and a lot of nutrients to grow.In addition,tumor-associated macrophages（TAMs）are the main immune cell types found in The tumor microenvironment（TME）of various cancer models.For growing tumors,macrophages with M2 phenotype have been found to promote the growth and invasion of tumor cells and trigger angiogenesis.It also reduces T cell activity.Therefore,it is of great significance for tumor therapy to develop nanosystems that inhibit energy metabolism of tumor cells and induce macrophage polarization.Based on this,we designed a nanoplatform for generating reactive oxygen species（ROS）（MnClPc-HSA@Gox NPs）.We coated manganese phthalocyanine complex（MnClPc）with human serum protein（HAS）and loaded glucose oxidase（GOx）onto MnClPc@HSA nanoparticles under ultrasonic and ice bath conditions.The HSA-based nanoplatform uses GOx to catalyze the decomposition of glucose to produce hydrogen peroxide and gluconic acid,and catalyzes H₂O₂ to ROS through the action of MnClPc.The experiment showed that,on the one hand,the nano platform blocked the glucose supply of tumor cells and inhibited the energy metabolism of tumor cells.On the other hand,the ROS produced mediate the polarization of TAMs,reversing the M2 type（anti-inflammatory type）into the M1 type（pro-inflammatory type）.Finally,good tumor inhibition effect was achieved.更多还原