Lymph node metastasis (LNM) is correlated with decreased survival, indicating high
tumor malignancy and being a potential source for subsequent fatal
metastases. Targeted
therapies inhibiting the formation of LNM, while eliminating established metastatic foci, could provide synergistic effects by reducing the incidence and growth of
metastasis. Based on the inhibitory activity of
cRGD peptide against the development of
metastasis, and the LNM targeting ability of systemically injected
drug-loaded polymeric
micelles, herein, we studied the capability of cRGD-installed polymeric
micelles incorporating the
platinum anticancer
drug (1,2-diaminocylohexane)platinum(II) (DACHPt) for cooperatively inhibiting the formation and progression of LNM. As cRGD-installed DACHPt-loaded
micelles (cRGD-DACHPt/m) presented similar size,
drug loading and surface charge to non-conjugated
micelles (MeO-DACHPt/m), the differences in the
biological performance of the
micelles were endorsed to the effect of the
ligand. In a syngeneic
melanoma model, both MeO-DACHPt/m and cRGD-DACHPt/m showed comparable antitumor activity against the primary
tumors and the established metastatic foci in lymph nodes. However, cRGD-DACHPt/m significantly enhanced the efficacy against LNM draining from primary
tumors through the effective inhibition of the spreading of
cancer cells. This improved inhibition was associated with the ability of cRGD-DACHPt/m to reduce the migration of
melanoma cells, which was higher than that of MeO-DACHPt/m, free cRGD and their combination. These results support our strategy of using cRGD-installed
micelles for attaining cooperative
therapies against LNM exploiting the inhibitory function of the
peptide and the cytotoxic effect of the
micelles.