Background: Lymph node metastasis increases the probability of cancer relapse and spread to other tissues even after resection of the primary tumor. Here we demonstrate nanoparticles (NPs) that efficiently transport chemotherapy to lymph nodes with metastasis and primary tumor for effective cancer treatment.
Materials and Methods: Nanoparticles (NPs) were formulated from poly (glycolide-co-lactide) using a modified single emulsion-solvent evaporation technique. The NPs were characterized for size, charge and surface morphology. Biodistribution of NPs into lymph nodes and tumors was determined after intravenous (IV) and subcutaneous (SQ) injection in a murine model of prostate cancer. Efficacy of paclitaxel (PTX) loaded NPs at inhibiting the progression of both established tumor and lymph node metastases were also evaluated.
Results: The formulated NPs which were 112 nm in size localized into all lymph nodes along a targeted lymphatic network after SQ injection (Fig.1A). Lymph nodes with metastasis showed a 6-fold greater NP accumulation compared to normal lymph nodes. The NPs ultimately entered the blood and accumulated into tumors at 14% injected dose/g of tumor (ID/GT) compared to 1% ID/GT when injected IV. A single SQ injection of PTX-loaded NPs (PTX-NP-SQ) in murine prostate cancer models with established tumors and lymph node metastasis decreased metastasis burden by 500% (Fig.1B) and increased tumor doubling time by 40% compared to IV injection (PTX-NP-IV). This resulted in 20% increase in average survival time compared to those injected intravenously.
Conclusions: These results demonstrate that NPs can effectively deliver therapeutics primary tumors and lymph node metastases for better cancer treatment.
