Design and Characterization of Endostatin-Loaded Nanoparticles for In Vitro Antiangiogenesis in Squamous Cell Carcinoma

Abstract

The aim of this study is to effectively enhance antitumor activities of endostatin by preparing polymeric nanocarriers. NMR and FT-IR spectra confirmed the successful grafting of the CHT-g-PEI and CHT-g-PEI-PEG-NH 2 conjugates. SEM micrographs confirmed the shape of endostatin-loaded nanoparticles to be spherical while both TEM and zeta size results showed nanoparticle's average size to be 100.6 nm having a positively charged surface with zeta potential of 7.95 mV. The concentrations of CHT and TPP as well as the changing pH conditions account for the increased swelling pattern of endostatin-loaded nanoparticles and influenced endostatin release in vitro. PEI increased the overall amine protonation while PEG aggravated endostatin encapsulation and release. Nanoparticles swell and release endostatin at acidic tumor pH of 6.8 compared to physiological pH of 7.4. The native CHT-g-PEI-PEG-NH 2 conjugate showed high cytocompatibility above 80% cell viability across tested formulations. Endostatin-loaded nanoparticles showed a significant reduction in cell viability across tested formulations, with 5.32% cell death at 125 g/mL and 13.36% at 250 g/mL following 24 hours' incubation period. Interestingly, more than a fourfold (61.68%) increment in cytotoxicity was observed at nanoparticle concentration of 1000 g/mL. It was concluded that CHT-g-PEI-PEG-NH 2 is an effective cargo for endostatin delivery with antiangiogenic effect in squamous cell carcinoma.

Recombinant Endostatin as a Potential Radiosensitizer in the Treatment of Non-Small Cell Lung Cancer

“…RE-loaded nanoparticles have also shown anti-angiogenic effects in vivo; for example, a folic acid-decorated chitosan nanoparticle successfully targeting squamous cell carcinoma (SCC) [ 89 , 90 , 91 ]. VEGFR-2 was successfully targeted in the blood brain barrier by Lu et al, using a dual receptor peptide functionalized polyethyleneimine nanocomplex for secretory RE delivery to malignant glioma [ 92 ].…”

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

“…In a previous study, CHT-g-PEI-PEG-NH2 nanoparticles were successfully synthesized for the effective delivery of ENT with a 4-fold increase in cytotoxicity against an oesophageal squamous cell carcinoma (OSCC) cell line (KYSE-30) [ 8 , 9 ]. Although significant cytotoxicity was achieved, the system was void on any specificity as a non-targeting approach.…”