Lymph
metastasis is a vital pathway of
cancer cell dissemination, and insidious
lymph node metastasis increases the risk of distant
cancer metastasis. Current
therapies for lymph
metastasis are largely restricted by limited targeting and penetration capacity. Herein, we report that an r9
cell-penetrating peptide-based
cabazitaxel nanovehicle (r9-CN) displays prominent lymph
metastasis targeting and deep penetration ability after
intravenous injection for effective anti-
metastasis therapy. Methods: The r9-CN and CN nanovehicles were prepared by thin film dispersion, using
DSPE-PEG2000 as the nano-carrier material and
cabazitaxel as the model drug to fabricate r9-modified nano-
micelles by self-assembly. The morphology, size, and stability in physiological solutions of r9-CN and CN were characterized. The targeting, biodistribution, deep penetration, and therapeutic efficacy of r9-CN and CN were systematically explored in vitro and in vivo. Results: The r9-CN nanovehicle consists of homogeneous particles with a mean diameter of 13 nm and zeta potential of +0.75 mV. Compared with the nanovehicle lacking the r9
peptide (CN), r9-CN exhibits long retention and deep penetration in the
tumor mass, and considerably enhances accumulation and flexible permeation in metastatic lymph nodes, thereby notably suppressing primary
tumor growth,
lymph node metastasis, and distant lung
metastasis. Conclusion: The cumulative findings reveal that r9-CN offers a promising delivery platform, enabling efficient lymph
metastasis targeting and deep penetration for effective anti-
metastasis therapy.