Antiangiogenic
cancer therapy based on nanoparticulate drug
delivery systems (nano-DDS) is emerging as a promising new approach besides the proved molecular-targeted
antiangiogenic agents. The current nano-DDS are restricted to the targeting to
tumor vascular endothelial cells, but seldom efforts have been made to target the
tumor vascular pericytes which are also actively involved in
tumor angiogenesis. In this study, we developed a new nano-DDS,
TH10 peptide (TAASGVRSMH) conjugated nanoparticles loading
docetaxel (TH10-DTX-NP) that can target the
NG2 proteoglycan highly expressed in
tumor vascular pericytes, for the investigation of therapeutic efficacy in the mice bearing B16F10-luc-G5
melanoma experimental lung
metastasis. The results demonstrated that TH10-DTX-NP achieved controlled drug release in PBS and the mixture of rat plasma and PBS (1:1, v/v), and exhibited favorable in vivo long-circulating feature.
TH10 peptide conjugation facilitated the nanoparticle internalization in pericytes via the interaction between TH10 and NG2 receptor, leading to more inhibition of pericyte viability and migration. TH10-conjugated nanoparticles could accurately target the vascular pericytes of B16F10-luc-G5 lung
metastasis, where DTX-induced pronounceable pericyte apoptosis. TH10-DTX-NP significantly prolonged the mice survival with no obvious toxicity, and this enhanced antitumor effect was closely related with the decreased pericyte density and microvessel density in the lung
metastases. The present research reveals the potency and significance of targeting
tumor vascular pericytes using nano-DDS in antiangiogenic
cancer therapy.