Targeted Delivery Of Hyaluronic Acid-Labeled Chitosan Nanoparticles Against Cd44 Overexpressed Endothelial Cell For Tumor Angiogenesis Therapy

Objective: RNA interference (RNAi)-based approaches hold great potential for cancer therapy. Here, we developed siRNA-incorporated chitosan nanoparticles coated with hyaluronic acid (HA-CH-NP/siRNA) to target CD44 receptor on the surface of tumor endothelial cells Methods: Size and zeta potential of HA-CH-NP were measured by light scattering with a particle size analyzer and Zeta Plus. Morphology of HA-CH-NP was observed by atomic force microscopy (AFM). HA-based selective binding of HA-CH-NP on the CD44 positive cells was assessed by flow cytometry and immunohistochemistry (IHC) analysis. Therapeutic efficacy was examined in orthotopic mouse models of ovarian carcinoma. PLXDC1 mRNA was quantified using real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, biological effect on angiogenesis (MCD), cell proliferation (Ki67), and apoptosis (TUNEL) in the tumor tissue were examined by IHC analysis. Results: HA-CH-NP/siRNA was 185 ± 10 nm in size and zeta potential was 26.4 mV, respectively. The loading efficiency of siRNA into HA-CH-NP/siRNA was up to 60%. We confirmed selective binding efficiency of HA-CH-NP/siRNA with CD44+ tumor endothelial cells was increased 2.1-fold compared to CH-NP/siRNA. PLXDC1 silencing using HA-CH-NP/siRNA significantly inhibited tumor growth in A2780 tumor growth in A2780 tumor-bearing mice compared to control (p Conclusion: This study demonstrated that HA-CH-NP/siRNA was a novel and highly selective delivery system for siRNA with potential for broad applications for tumor angiogenesis therapy. Citation Format: Gahee Kim, Heedong Han. Targeted delivery of hyaluronic acid-labeled chitosan nanoparticles against CD44 overexpressed endothelial cell for tumor angiogenesis therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2183. doi:10.1158/1538-7445.AM2017-2183