Self-assembled peptide-dye nanostructures for in vivo tumor imaging and photodynamic toxicity
Self-assembled peptide-dye nanostructures for in vivo tumor imaging and photodynamic toxicity
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DOI：
10.1038/s44303-024-00008-4
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发表时间：
2024-03
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通讯作者：
R. Borum;Maurice Retout;Matthew N Creyer;Yu-Ci Chang;Karlo Gregorio;Jesse V. Jokerst
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作者：
R. Borum;Maurice Retout;Matthew N Creyer;Yu-Ci Chang;Karlo Gregorio;Jesse V. Jokerst
我们报告了iRGD肽和亚甲蓝染料通过静电和疏水堆积的非共价组装。这些产生的纳米材料可以与癌细胞结合，用光声信号对它们进行成像，然后通过光动力疗法对其进行治疗。我们首先评估了材料的光学性质和物理性质。然后，我们评估了它们在活细胞靶向、体内成像和体内光动力毒性方面的效用。我们通过向肽中添加天冬氨酸（DD）或色氨酸双联体（WW）来分别促进与亚甲蓝的静电或疏水堆积，从而调整iRGD的性能。iRGD-DD导致150 nm的分支纳米颗粒，但iRGD-WW产生200 nm的纳米球。支化颗粒具有红移至720 nm的吸收峰，适合于光声信号。纳米球在680 nm处具有类似于单体亚甲蓝的峰。在连续照射后，纳米球和分支纳米颗粒导致SKOV-3细胞中的活性氧相对于游离亚甲蓝在等摩尔浓度下增加116.62%和94.82%，表明光动力学毒性。通过竞争性抑制验证靶向摄取。最后，我们使用体内生物发光信号来监测肿瘤负荷和光动力疗法的效果：纳米球与对照相比几乎没有影响（p= 0.089），但分支纳米颗粒使SKOV-3肿瘤负荷减缓了75.9%（p< 0.05）。
We report noncovalent assemblies of iRGD peptides and methylene blue dyes via electrostatic and hydrophobic stacking. These resulting nanomaterials could bind to cancer cells, image them with photoacoustic signal, and then treat them via photodynamic therapy. We first assessed the optical properties and physical properties of the materials. We then evaluated their utility for live cell targeting, in vivo imaging, and in vivo photodynamic toxicity. We tuned the performance of iRGD by adding aspartic acid (DD) or tryptophan doublets (WW) to the peptide to promote electrostatic or hydrophobic stacking with methylene blue, respectively. The iRGD-DD led to 150-nm branched nanoparticles, but iRGD-WW produced 200-nm nano spheres. The branched particles had an absorbance peak that was redshifted to 720 nm suitable for photoacoustic signal. The nanospheres had a peak at 680 nm similar to monomeric methylene blue. Upon continuous irradiation, the nanospheres and branched nanoparticles led to a 116.62% and 94.82% increase in reactive oxygen species in SKOV-3 cells relative to free methylene blue at isomolar concentrations suggesting photodynamic toxicity. Targeted uptake was validated via competitive inhibition. Finally, we used in vivo bioluminescent signal to monitor tumor burden and the effect of for photodynamic therapy: The nanospheres had little impact versus controls (p= 0.089), but the branched nanoparticles slowed SKOV-3 tumor burden by 75.9% (p< 0.05).