Abstract
Abstract Colorectal cancer is a popular cancer type all over the world. Among various treatment regimen, oxaliplatin (Oxa) is approved in combination with 5-fluorouracil (5-FU) and leucovorin (FOLFOX) as the first-line therapy for colorectal cancer of metastatic or advanced stage. MicroRNAs (miRs) may target genes critical for regulating tumor proliferation and invasion. Among different miRs, miR-c has been proved to induce apoptosis, inhibit proliferation and epithelial-mesenchymal transition of cancer cells. Peptide-modified nanoparticles, which are capable of increasing cellular uptake and targeting to specific receptors, are well suitable for delivering Oxa and miR. Moreover, coating pH-sensitive polymers to the outer layer of peptide-modified nanoparticles may enhance specific targeting to the acidic tumor sites. Physicochemical characterization, cellular uptake, cytotoxicity, migration assay, and western blotting studies of these nanoparticle formulations have been performed. Our results indicated that these pH-sensitive and peptide-modified nanoparticles displayed a narrow size distribution. The cellular uptake of peptide-modified nanoparticles was found to be greater than that of naked nanoparticles. Besides, the cellular uptake of pH-sensitive nanoparticles was significantly increased at pH 6.0 compared to that at pH 7.4, suggesting the successful pH-responsive property of these delivery systems. Furthermore, the combined treatment of miR-c and Oxa by peptide-modified nanoparticles increased the cytotoxicity of Oxa to colorectal cancer cells. We demonstrated that the upregulation of apoptosis pathway and the downregulation of β-catenin pathway were accounted for the efficient antitumor effect. In conclusion, the delivery of miR-c and Oxa in pH-sensitive and peptide-modified nanoparticles may provide a novel and potential strategy for colorectal cancer treatment. Citation Format: Yu-Li Lo, Y.C. Chen, C.H. Chang, W.H. Tseng, C.S. Wang. Tumor-targeted and pH-shiftable nanoparticles to encapsulate oxaliplatin and microRNA for colorectal cancer therapy [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A100. doi:10.1158/1535-7163.TARG-19-A100
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