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

Abstract

Highlights Small-sized trastuzumab-targeted micelles (T-MP) were engineered using a surfactant-stripping approach that yielded concentrated phthalocyanines with strong near infrared absorption. T-MP accumulated more in the lymph node (LN) metastases of orthotopic colorectal cancer 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. 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. Supplementary Information The online version contains supplementary material available at 10.1007/s40820-021-00666-8.

Affimer Tagged Cubosomes: Targeting of Carcinoembryonic Antigen Expressing Colorectal Cancer Cells Using In Vitro and In Vivo Models

“…62 Thus, these data indicate that the targeted delivery of Cu-Cb-Af has a positive impact on the mice heath and restricted the tumor growth. It would also be of value to assess in the future this effect in orthotopic models, especially of locally disseminated disease, 63 for which systemic targeted therapeutics have real potential to impact on clinical outcomes. Drug safety is assessed based on its effect on vital organs, 40,41,64 and one such method to analyze the toxicity is an in-depth tissue study.…”

Cancer nanomedicine in preoperative therapeutics: Nanotechnology-enabled neoadjuvant chemotherapy, radiotherapy, immunotherapy, and phototherapy

“…In addition to the primary tumor, another preoperative imaging and surgical target is the lymph nodes (LNs). Accurate preoperative imaging of LNs and their acquisition during and after surgery is of great significance to grading, treatment, and prognosis evaluation for tumors, especially in patients with gastric cancer [ 164 , 165 ]. Some studies have indicated that obtaining an adequate number of dissected lymph nodes is positively associated with improved survival rate [ 166 , 167 ].…”

“…This puts a higher demand on the LN imaging. Traditional optical dyes (such as Evans blue, indocyanine green, and IR820) and radiolabeled-tracer-based LN imaging have clinical limitations due to their insufficient accumulation, rapid clearance, and short retention time [ 165 , 168 ]. The advanced development of nanotechnology brings many new opportunities to preoperative LN imaging.…”

Research Progress of Photothermal Nanomaterials in Multimodal Tumor Therapy

“…With further research on PCs, it was found that PC nanomaterials also exhibit high PCE after irradiation with NIR light, giving them great potential in the application of PTT ( 208 , 209 ). Feng et al ( 55 ) designed T-MP nanoplatforms based on HER2 and targeted micellular PC. The results of in vivo and in vitro antitumor experiments showed that after 808-nm laser irradiation, the killing rate of HT-29 cells in the T-MP group was much higher than that in the control group.…”