Targeted Micellar Phthalocyanine for Lymph Node Metastasis Homing and Photothermal Therapy in an Orthotopic Colorectal Tumor Model

Tumor lymph node (LN) metastasis seriously affects the treatment prognosis. Studies have shown that nanoparticles with size of sub-50 nm can directly penetrate into LN metastases after intravenous administration. Here, we speculate through introducing targeting capacity, the nanoparticle accumulation in LN metastases would be further enhanced for improved local treatment such as photothermal therapy. Trastuzumab-targeted micelles (< 50 nm) were formulated using a unique surfactant-stripping approach that yielded concentrated phthalocyanines with strong near-infrared absorption. Targeted micellar phthalocyanine (T-MP) was an effective photothermal transducer and ablated HT-29 cells in vitro. A HER2-expressing colorectal cancer cell line (HT-29) was used to establish an orthotopic mouse model that developed metastatic disease in mesenteric sentinel LN. T-MP accumulated more in the LN metastases compared to the micelles conjugated with control IgG. Following surgical resection of the primary tumor, minimally invasive photothermal treatment of the metastatic LN with T-MP, but not the control micelles, extended mouse survival. Our findings demonstrate for the first time that targeted small-sized nanoparticles have potential to enable superior paradigms for dealing with LN metastases.