5-氨基乙酰丙酸 (5-ALA) 是卟啉 IX (PpIX) 的前药。 5-ALA的缺点包括稳定性差、消除快、生物利用度差、细胞渗透力弱等，这些都大大降低了基于5-ALA的光动力疗法（PDT）的临床效果。目前，利用金纳米粒子（AuNP）作为载体构建了一种新型靶向纳米系统，分别通过金硫键和离子键负载CSNIDARAC（CC9）靶向肽和5-ALA，然后包裹在聚乳酸乙醇酸（PLGA）中纳米粒子通过自组装来提高抗肿瘤效果并减少副作用。利用紫外-可见光、傅里叶变换红外光谱和X射线光电子能谱验证了ALA/CC9@ AuNPs-PLGA NPs的成功制备。分析显示其球形度良好，粒径约为140 nm，Zeta电位为10.11 mV，在弱酸环境下具有缓控释放特性。共聚焦显微镜揭示了纳米颗粒通过主动内化 CC9 并避免 RAW264.7 细胞的吞噬作用来靶向 NCL-H460 细胞，实时荧光成像揭示了荷瘤小鼠中肿瘤的靶向。与游离 5-ALA 相比，该纳米系统通过增加 PpIX 和活性氧的产生来诱导线粒体途径凋亡，从而表现出增强的抗癌活性。在三维培养的细胞中，随着肿瘤球完整性的丧失，一致地观察到抗肿瘤功效。在异种移植肿瘤模型中通过降低生长速率和增加肿瘤细胞凋亡证明了更有效的抗肿瘤功效。组织学分析表明该系统无毒，降低了5-ALA的肝毒性。因此，ALA/CC9@AuNPs-PLGA NPs通过载体级联传递5-ALA，通过被动增强渗透性和保留作用以及主动靶向，对肿瘤积累和PDT具有优异的效果。这种癌症治疗的创新策略在实施之前需要更多的临床试验。版权所有 © 2024。由 Elsevier B.V. 出版。

5-Aminolevulinic acid (5-ALA) is a prodrug of porphyrin IX (PpIX). Disadvantages of 5-ALA include poor stability, rapid elimination, poor bioavailability, and weak cell penetration, which greatly reduce the clinical effect of 5-ALA based photodynamic therapy (PDT). Presently, a novel targeting nanosystem was constructed using gold nanoparticles (AuNPs) as carriers loaded with a CSNIDARAC (CC9)-targeting peptide and 5-ALA via Au-sulphur and ionic bonds, respectively, and then wrapped in polylactic glycolic acid (PLGA) NPs via self-assembly to improve the antitumor effects and reduce the side effect. The successful preparation of ALA/CC9@ AuNPs-PLGA NPs was verified using ultraviolet-visible, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The analyses revealed good sphericity with a particle size of approximately140 nm, Zeta potential of 10.11 mV, and slow-controlled release characteristic in a weak acid environment. Confocal microscopy revealed targeting of NCL-H460 cells by NPs by actively internalising CC9 and avoiding the phagocytic action of RAW264.7 cells, and live fluorescence imaging revealed targeting of tumours in tumour-bearing mice. Compared to free 5-ALA, the nanosystem displayed amplified anticancer activity by increasing production of PpIX and reactive oxygen species to induce mitochondrial pathway apoptosis. Antitumor efficacy was consistently observed in three-dimensionally cultured cells as the loss of integrity of tumour balls. More potent anti-tumour efficacy was demonstrated in xenograft tumour models by decreased growth rate and increased tumour apoptosis. Histological analysis showed that this system was not toxic, with lowered liver toxicity of 5-ALA. Thus, ALA/CC9@AuNPs-PLGA NPs deliver 5-ALA via a carrier cascade, with excellent effects on tumour accumulation and PDT through passive enhanced permeability and retention action and active targeting. This innovative strategy for cancer therapy requires more clinical trials before being implemented.Copyright © 2024. Published by Elsevier B.V.