Speakers - CWC 2023

Abstract

Background: Pancreatic cancer remains one of the most lethal cancers largely due to the inefficient delivery of therapeutics. Nanomaterials have been extensively investigated as drug delivery platforms, showing improved drug pharmacodynamics and pharmacokinetics. Meanwhile, smaller-sized nanomaterials have shown improved tumor delivery and retention in various tumors, including pancreatic tumors, suggesting their potential in enhancing drug delivery.

Objective: To investigate the pancreatic cancer cell targeting drug carriers using ultrafine iron oxide nanoparticle (uIONP) loading insulin-like growth factor 1 (IGF-1) and subsequently induced cell apoptosis.

Methods: An uIONP was used to encapsulate 7-ethyl-10-hydroxyl camptothecin (SN38), the water-insoluble active metabolite of pancreatic cancer chemotherapy drug irinotecan. IGF-1 was conjugated to uIONP as a ligand for targeting pancreatic cancer cells overexpressing the IGF-1 receptor (IGF1R). The SN38 loading and release profile was characterized by incubating uIONP/SN38 in buffered solutions of pH 5.5, 6.5, and 7.4, mimicking the lysosomal, tumor interstitial, and physiological environment, respectively. Then, followed conjugation of IGF-1 and NIR830 dye to uIONP. The MiaPaCa-2 and Panc02 pancreatic cancer cells targeting, cytotoxicity assays, and cell apoptosis of IGF1-uIONP/SN38 were tested in vitro. Statistical significance was determined by a two-tailed unpaired t-test when comparison of uIONP before and after SN38 loading and conjugation of IGF-1. The level of significance was set at p<0.05.

Results: IGF1-uIONP/SN38 demonstrated a stable drug loading in physiological pH with the loading efficiency of 68.2±3.5% (SN38/Fe, wt%) and <7% release for 24 h. In tumor-interstitial- and lysosomal-mimicking pH (6.5 and 5.5), 52.2 and 91.3% of encapsulated SN38 were released over 24 h. The IGF1-uIONP/SN38 exhibited specific receptor-mediated cell targeting and cytotoxicity to MiaPaCa-2 and Panc02 pancreatic cancer cells with IC50 of 11.8±2.3 and 20.8±3.5 nM, respectively, but not to control HEK293 human embryonic kidney cells.

Conclusion: IGF1-uIONP significantly improved the targeted SN38 delivery to pancreatic cancer cells, holding the potential for in vivo theranostic applications.