Abstract
Mitoxantrone (MTO) is used to treat certain types of cancer, mostly metastatic cancer. While the drug has poor aqueous solubility and high side effects. Self-assembly nanocrystal is a novel lymphatic targeting delivery system. In our study, MTO self-assembly nanocrystal (MTO NC) was successfully prepared to improve lymphatic targeting ability and reduce its toxicity. MTO NCs had small size, stable potential, and uniform distribution. The average particle size of MTO NCs was less than 100nm with the 0.218 PDI and - 6.6mV the Zeta potential value. TEM images showed that MTO NCs had a sphere-like morphology with smooth surface and uniform distribution; Atomic force microscopy (AFM) images gave a 3D surface of MTO NCs. Polarizing microscope micrograph (PLM) of MTO NCs in lymph nodes demonstrated the crystal structure of MTO NCs when it was exposed to physiological condition. Transmission electron microscopy showed the presence of MTO NCs in mice lymph nodes. Pharmacokinetic parameters of MTO strongly demonstrated that MTO NCs could target the lymph nodes after subcutaneous injection. Moreover, tissue distribution results indicated that MTO NCs were mainly absorbed by the lymphatics and reduced system toxicity. Finally, a lymphatic metastasis mice model was established to precede the pharmacodynamics of MTO NCs, and using MTO liposomes as a reference preparation, the inhibitory effect of MTO NCs on lymphatic metastasis was markedly higher. Briefly, MTO NCs, as a novel self-assembled lymphatic targeting system, can accumulate in the metastatic lymph nodes and lead anticancer drug to kill cancer cells and control lymphatic metastasis with extremely low systemic toxicity.
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