NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Harbin Medical University, Harbin, 150001, P. R. China.
Heilongjiang Key Laboratory of Scientific Research in Urology, Harbin Medical University, Harbin, 150001, P. R. China.
Small. 2023 Jun;19(25):e2300060. doi: 10.1002/smll.202300060. Epub 2023 Mar 17.
Nanoscale drug carriers play a crucial role in reducing side effects of chemotherapy drugs. However, the mononuclear phagocyte system (MPS) and the drug protonation after nanoparticles (NPs) burst release still limit the drug delivery efficiency. In this work, a self-disguised Nanospy is designed to overcome this problem. The Nanospy is composed of: i) poly (lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG) loading doxorubicin is the core structure of the Nanospy. ii) CD47 mimic peptides (CD47p) is linked to NPs which conveyed the "don't eat me" signal. iii) 4-(2-aminoethyl) benzenesulfonamide (AEBS) as the inhibitor of Carbonic anhydrase IX (CAIX) linked to NPs. Briefly, when the Nanospy circulates in the bloodstream, CD47p binds to the regulatory protein α (SIRPα) on the surface of macrophages, which causes the Nanospy escapes from phagocytosis. Subsequently, the Nanospy enriches in tumor and the AEBS reverses the acidic microenvironment of tumor. Due to above characteristics, the Nanospy reduces liver macrophage phagocytosis by 25% and increases tumor in situ DOX concentration by 56% compared to PLGA@DOX treatment. In addition, the Nanospy effectively inhibits tumor growth with a 63% volume reduction. This work presents a unique design to evade the capture of MPS and overcomes the influence of acidic tumor microenvironment (TME) on weakly alkaline drugs.
纳米药物载体在降低化疗药物的副作用方面发挥着关键作用。然而，单核吞噬细胞系统（MPS）和纳米颗粒（NPs）爆裂释放后的药物质子化仍然限制了药物递送效率。在这项工作中，设计了一种自伪装的 Nanospy 来克服这个问题。Nanospy 由以下部分组成：i）载有多柔比星的聚乳酸-聚乙二醇（PLGA-PEG）是 Nanospy 的核心结构。ii）CD47 模拟肽（CD47p）连接到 NPs 上，传递“不要吃我”的信号。iii）4-（2-氨基乙基）苯磺酰胺（AEBS）作为碳酸酐酶 IX（CAIX）的抑制剂连接到 NPs 上。简而言之，当 Nanospy 在血液中循环时，CD47p 与巨噬细胞表面的调节蛋白 α（SIRPα）结合，导致 Nanospy 逃避吞噬作用。随后，Nanospy 在肿瘤中富集，AEBS 逆转肿瘤的酸性微环境。由于上述特点，与 PLGA@DOX 治疗相比，Nanospy 使肝脏巨噬细胞的吞噬作用减少了 25%，并使肿瘤原位 DOX 浓度增加了 56%。此外，Nanospy 有效抑制肿瘤生长，体积减少 63%。这项工作提出了一种独特的设计来逃避 MPS 的捕获，并克服酸性肿瘤微环境（TME）对弱碱性药物的影响。
