Tumor-Targeted Polydopamine-Based Nanoparticles for Multimodal Mapping Following Photothermal Therapy of Metastatic Lymph Nodes

• Published in: International journal of nanomedicine 2022-01, Vol.17, p.4659-4675
• Main Authors: Liang, Yanrui, Guo, Weihong, Li, Chuangji, Shen, Guodong, Tan, Haoxian, Sun, Peiwen, Chen, Zhian, Huang, Huilin, Li, Zhenhao, Li, Zhenyuan, Ren, Yingxin, Li, Guoxin, Hu, Yanfeng
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents; Aqueous solutions; Cell Line, Tumor; Contrast Media; Dopamine; Ethylenediaminetetraacetic acid; Flow cytometry; Fluorescence; Fluorescent Dyes; Gastric cancer; Indoles; Integrin beta3; Integrins; Lasers; Ligands; lymph node mapping; Lymph Nodes - diagnostic imaging; Lymphatic system; Magnetic resonance imaging; Metastasis; metastatic lymph node; Mice; Microscopy; multimodal imaging; Nanoparticles; Original Research; Phototherapy - methods; Photothermal Therapy; Polyethylene glycol; Polyethylene Glycols; Polymerization; Polymers; Polyols; Stomach Neoplasms; Tomography; Tumors
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S367975

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 α β3 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.