Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, Southern Medical University, Guangzhou, People's Republic of China.
The First School of Clinical Medicine, Southern Medical University, Guangzhou, People's Republic of China.
Int J Nanomedicine. 2022 Sep 29;17:4659-4675. doi: 10.2147/IJN.S367975. eCollection 2022.
Lymphadenectomy with lymph node (LN) mapping is essential for surgical removal of solid tumors. Existing agents do not provide accurate multimodal mapping and antitumor therapy for metastatic LNs; therefore, we fabricated a polydopamine (PDA) nanoparticle (NP)-based tumor-targeted LN mapping agent capable of multimodal mapping and guided photothermal therapy (PTT) for metastatic LNs.
PDA NPs modified with polyethylene glycol (PEG) were obtained by polymerization under alkaline conditions. The PEG-PDA NPs were loaded with the circular tripeptide Arg-Gly-Asp (cRGD) to achieve tumor-targeting capacity and with the fluorescent dye IR820 and magnetic resonance imaging (MRI) contrast Gd(NH) for in situ detection. The resulting cRGD-PEG-PDA@IR820/Gd(NH) (cRGD-PPIG) NPs were tested for their biosafety and metastatic LN mapping ability. They were drained specifically into LNs and selectively taken up by gastric MKN45 cells via αβ3 integrin-mediated endocytosis.
This phenomenon enabled MR/optical/near-infrared fluorescence multimodal metastatic LN mapping, guiding the creation of accurate and highly efficient PTT for gastric cancer metastatic LNs in mice.
In summary, we fabricated tumor-targeted cRGD-PPIG NPs with MR/optical/near-infrared fluorescence multimodal metastatic LN mapping capacity for surgery and efficient PTT guidance post-surgery.
淋巴结切除术和淋巴结(LN)绘图对于实体瘤的外科切除至关重要。现有的药物不能为转移性 LN 提供准确的多模态绘图和抗肿瘤治疗;因此,我们制造了一种基于聚多巴胺(PDA)纳米颗粒(NP)的肿瘤靶向 LN 绘图剂,该剂能够进行多模态绘图和指导转移性 LN 的光热治疗(PTT)。
通过碱性条件下的聚合获得了聚乙二醇(PEG)修饰的 PDA NPs。将 PEG-PDA NPs 负载环状三肽 Arg-Gly-Asp(cRGD)以实现肿瘤靶向能力,并负载荧光染料 IR820 和磁共振成像(MRI)造影剂 Gd(NH),用于原位检测。对所得的 cRGD-PEG-PDA@IR820/Gd(NH)(cRGD-PPIG)NPs 进行了生物安全性和转移性 LN 绘图能力的测试。它们通过 αβ3 整联蛋白介导的内吞作用特异性引流到 LN 中,并被胃 MKN45 细胞选择性摄取。
这种现象实现了磁共振/光学/近红外荧光多模态转移性 LN 绘图,指导了小鼠胃癌转移性 LN 的精确和高效 PTT 的创建。
总之,我们制造了具有磁共振/光学/近红外荧光多模态转移性 LN 绘图能力的肿瘤靶向 cRGD-PPIG NPs,用于手术,并在手术后指导高效的 PTT。