Size-Dependent Effect of Indocyanine Green Nanoimaging Agent for Metastatic Lymph Node Detection.

Identification of metastatic lymph nodes is a crucial step in lymph node dissection to prevent further cancer spread and recurrence. However, the current limitations in metastatic lymph node detection often result in extensive resection of normal lymph nodes, leading to serious complications. The clinical application of indocyanine green (ICG) as a tool for lymph node detection is challenging because of its short plasma half-life and rapid light-induced decomposition and clearance. To overcome this limitation, we used polydopamine nanoparticles (PNs) as carriers for ICG and screened for the optimal particle size for detecting metastatic lymph nodes. ICG/PNs with sizes of 80, 160, 300, and 600 nm were synthesized, and their ICG loading efficiency, physical stability, and lymph node distribution were evaluated. The ICG absorbed on the PNs was found to be protected from light degradation, and its retention at the lymph nodes was improved. Notably, the ICG/PNs favored the fluorescence signal at the metastatic lymph nodes compared to the nonmetastatic lymph nodes. Among the tested particle sizes, the 80-nm ICG/PN showed a higher distribution in the metastatic lymph nodes. This study suggests that the 80-nm ICG/PN is a potentially valuable reagent for the detection and diagnosis of lymph node metastasis.

Nanoparticles for Lymph Node-Directed Delivery.

Lymph nodes are organs that control immune cells and provide a major pathway for primary tumors to metastasize. A nanoparticles-based strategy has several advantages that make it suitable for achieving effective lymphatic delivery. First, the size of nanoparticles can be tailored to meet a size range appropriate for lymphatic migration. In addition, functionalized nanoparticles can target cells of interest for delivery of drugs or imaging probes. Existing lymph node contrast agents map all lymph nodes regardless of metastasis status; however, by using nanoparticles, it is possible to selectively target lymphatic metastases. Moreover, using functionalized nanoparticles, it is possible to specifically deliver anticancer drugs to metastatic lymph nodes. In this review, we introduce the use of nanoparticles for lymphatic mapping, in particular highlighting design considerations for detecting metastatic lymph nodes. Furthermore, we assess trends in lymph node-targeting nanoparticles in clinical practice and suggest future directions for lymph node-targeting nanoparticles.

Blood-declustering excretable metal clusters assembled in DNA matrix.

We report polymeric DNA-supported gold clusters that achieve interparticle plasmon-coupling, generate immunotherapeutic effects at the tumor tissue, but decluster in the bloodstream. As immunostimulating DNA, we used polyCpG DNA, which could act as a supporting matrix for metal clusters, enabling the clusters to decluster in the bloodstream. We constructed polyCpG-supported gold nanoclusters (AuPCN). For comparison with AuPCN, monomer CpG-bound gold nanoparticles (AuMC) were used. Unlike AuMC, AuPCN showed an interparticle plasmon-coupling effect and a higher light-to heat conversion efficiency. In the serum, AuPCN declustered to subunits. The CT26 tumor rechallenge of mice pretreated with AuPCN(+NIR) was followed by 0% tumor recurrence and 100% survival for up to 80 days. Compared with other groups, AuPCN(+NIR)-treated mice revealed greater cytotoxic T cell-infiltration in distant tumors and higher memory T cells in the lymph nodes. Until 7 days post-dose, the urinary excretion of Au was observed in the AuPCN-treated group, but not in the Au nanoparticle-treated mice. Although we used gold clusters and concatemeric immunostimulatory CpG as components of AuPCN, the concept of declustering in the bloodstream can be applied to design other functional DNA scaffold-based metal clusters with reduced concerns for long-term retention in the body.