In Vitro and In Vivo Evaluation of a Cyclic LyP-1-Modified Nanosystem for Targeted Endostatin Delivery in a KYSE-30 Cell Xenograft Athymic Nude Mice Model

This work investigated the use of LyP-1 as a homing peptide for p32 receptor targeting on the surface of an endostatin (ENT)-loaded chitosan-grafted nanosystem intended for intracellular delivery of ENT and mitochondrial targeting in a squamous cell carcinoma (SCC) cell line (KYSE-30) model. The angiogenic factors for VEGF-C and MMP2 were assessed with in vivo evaluation of the nanosystem upon ENT release and tumor necrosis in nude mice with a KYSE-30 cell xenograft. The LyP-1-modified nanosystem revealed a three-fold decrease in proliferation at 1000 mu g/mL compared with the control and facilitated receptor-mediated cellular uptake and internalization. In addition, targeting of the Lyp-1-functionalized nanosystem to mitochondrial and nuclear proteins in vitro and in vivo was achieved. Up to 60% inhibition of KYSE-30 cell migration was observed and the expressions of VEGF-C and MMP-2 as angiogenic markers were reduced 3- and 2-fold, respectively. A marked reduction in tumor mass was recorded (43.25%) with the control, a 41.36% decrease with the nanoparticles and a 61.01% reduction with the LyP-1-modified nanosystem following treatment in mice. The LyP-1-functionalized nanosystem targeted tumor lymphatics, instigated nuclear rupture and mitochondrial distortion, and decreased cell proliferation and migration with inhibition of VEGF-C and MMP2 expression.

Automated summary

This study investigated the use of LyP-1 as a homing peptide for p32 receptor targeting in a nanosystem loaded with endostatin for intracellular delivery and mitochondrial targeting in squamous cell carcinoma. The LyP-1-modified nanosystem showed reduced cell proliferation, increased receptor-mediated cellular uptake and internalization, and targeted mitochondrial and nuclear proteins. Additionally, the nanosystem inhibited cell migration and reduced the expression of angiogenic markers. The LyP-1-functionalized nanosystem also led to a significant reduction in tumor mass.