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Manganese(III) Phthalocyanine Complex Nanoparticle-Loaded Glucose Oxidase to Enhance Tumor Inhibition through Energy Metabolism and Macrophage Polarization
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2024-03-07 , DOI: 10.1021/acsabm.3c01251
Zhaoyang Liu 1 , Chao Li 1 , Yushi Cao 1 , Xin Xu 1 , Zhiguo Zhou 1 , Jing Du 2 , Shiping Yang 1 , Hong Yang 1
Affiliation  

Elevated levels of reactive oxygen species (ROS) have demonstrated efficacy in eliminating tumor cells by modifying the tumor microenvironment and inducing the polarization of tumor-associated macrophages (TAMs). Nevertheless, the transient nature and limited diffusion distance inherent in ROS present significant challenges in cancer treatment. In response to these limitations, we have developed a nanoparticle (MnClPc–HSA@GOx) that not only inhibits tumor energy metabolism but also facilitates the transition of TAMs from the M2 type (anti-inflammatory type) to the M1 type (proinflammatory type). MnClPc–HSA@GOx comprises a manganese phthalocyanine complex (MnClPc) enveloped in human serum albumin (HSA), with glucose oxidase (GOx) loaded onto MnClPc@HSA nanoparticles. GOx was employed to catalyze the decomposition of glucose to produce H2O2 and gluconic acid. Additionally, in the presence of MnClPc, it catalyzes the conversion of H2O2 into O2 and 1O2. Results indicate that the nanoparticle effectively impedes the glucose supply to tumor cells and suppresses their energy metabolism. Simultaneously, the ROS-mediated polarization of TAMs induces a shift from M2 to M1 macrophages, resulting in a potent inhibitory effect on tumors. This dual-action strategy holds promising clinical inhibition applications in the treatment of cancer.

中文翻译:


锰(III)酞菁复合物纳米颗粒负载葡萄糖氧化酶通过能量代谢和巨噬细胞极化增强肿瘤抑制



活性氧(ROS)水平升高已被证明可以通过改变肿瘤微环境和诱导肿瘤相关巨噬细胞(TAM)的极化来消除肿瘤细胞。然而,ROS 固有的短暂性和有限的扩散距离给癌症治疗带来了重大挑战。针对这些限制,我们开发了一种纳米颗粒(MnClPc–HSA@GOx),它不仅能抑制肿瘤能量代谢,还能促进TAM从M2型(抗炎型)向M1型(促炎型)的转变。 MnClPc–HSA@GOx 包含包裹在人血清白蛋白(HSA)中的锰酞菁复合物(MnClPc),以及负载到 MnClPc@HSA 纳米颗粒上的葡萄糖氧化酶(GOx)。 GOx用于催化葡萄糖分解产生H 2 O 2和葡萄糖酸。此外,在MnClPc 存在的情况下,它可以催化H 2 O 2转化为 O 2 -1 O 2 。结果表明,纳米颗粒有效地阻止了肿瘤细胞的葡萄糖供应并抑制了它们的能量代谢。同时,ROS 介导的 TAM 极化诱导巨噬细胞从 M2 转变为 M1,从而对肿瘤产生有效的抑制作用。这种双重作用策略在癌症治疗中具有广阔的临床抑制应用前景。
更新日期:2024-03-07
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