Accurate sequential detection of primary tumor and metastatic lymphatics using a temperature-induced phase transition nanoparticulate system

Abstract

Primary tumor and tumor-associated metastatic lymphatics have emerged as new targets for anticancer therapy, given that these are difficult to treat using traditional chemotherapy. In this study, docetaxel-loaded Pluronic nanoparticles with Flamma™ (FPR-675, fluorescence molecular imaging dye; DTX/FPR-675 Pluronic NPs) were prepared using a temperature-induced phase transition for accurate detection of metastatic lymphatics. Significant accumulation was seen at the primary tumor and in metastatic lymph nodes within a short time. Particle size, maximum drug loading capacity, and drug encapsulation efficiency of the docetaxel-loaded Pluronic NPs were approximately 10.34±4.28 nm, 3.84 wt%, and 94±2.67 wt%, respectively. Lymphatic tracking after local and systemic delivery showed that DTX/FPR-675 Pluronic NPs were more potent in tumor-bearing mice than in normal mice, and excised mouse lymphatics showed stronger near-infrared fluorescence intensity on the tumor-bearing side than on the non-tumor-bearing side at 60 minutes post-injection. In vivo cytotoxicity and efficacy data for the NPs demonstrated that the systemically administered NPs caused little tissue damage and had minimal side effects in terms of slow renal excretion and prolonged circulation in tumor-bearing mice, and rapid renal excretion in non-tumor-bearing mice using an in vivo real-time near-infrared fluorescence imaging system. These results clearly indicate that docetaxel-loaded Pluronic NPs could provide a strategy to achieve effective cancer therapy by simultaneous delivery to primary tumors, tumor lymphatics, and tumor-associated metastatic lymphatics.

Light-Responsive Polymeric Micellar Nanoparticles with Enhanced Formulation Stability

“…After 24 h, they were rinsed twice with DPBS (pH 7.4, with Ca 2+ , Mg 2+ ) to eliminate the remaining samples. 25 μL of the MTT reagent (5 mg/mL in media) was then added and incubated further for 4 h at 37 °C [ 51 , 52 ]. Thereafter, the purple precipitates (formazan crystals) were added and dissolved by adding 200 μL of DMSO.…”

Lymph node metastasis in cancer progression: molecular mechanisms, clinical significance and therapeutic interventions

“…Some studies have sought to apply theranostic approaches to target LNM. Oh et al 411 employed a combination of docetaxel-loaded Pluronic nanoparticles and the molecular imaging dye FPR-675 such that the delivery of both metastatic LNs and primary tumors would enable effective imaging and treatment. Cai et al 412 also prepared hybrid nanocomposite materials that were used for the multimodal imaging-guided photothermal treatment of LNM.…”