Abstract 4147: Chitosan luminescent rare-earth doped nanoparticles as cancer cell tracking for imaging tumors and their immune response
Authors: Osorio-Arciniega Rodrigo , Lucero-Meza Eduardo , Can-Uc Bonifacio , Rocha-Mendoza Israel , Fournier Pierrick G.J. , Hirata Gustavo A , Juarez Patricia 
Published: March 2024

Background: Cancer is a group of diseases characterized by the unregulated growth of cells, which can be hard to diagnose due to the high false negatives or positives derived from technical and human mistakes.The detection of solid tumors during resection surgery is also a common issue, so contrast agents are used for both cancer diagnosis and tumor visualization during surgery, facilitating the tumor resection procedure. Nevertheless, they cause long-term problems because they accumulate in specific tissues, low penetration, and rapid clearance from the circulation. It is necessary to study new contrast agents that improve tumor detection to address these issues.Here, we synthesized two different kinds of luminescent nanoparticles (LNPs) conjugated with chitosan (Ch) and functionalized with folic acid (FA) for breast cancer detection. We compared in vitro its physicochemical characteristics and effects on the proliferation of cancer cells. Evaluated its impact on the immune system in vivo and implemented a differential imaging process to resemble a refined 3D visualization of cluster cells using Light Sheet Microscopy.

Results: Luminescent nanoparticles (LNPs) synthesized by sol-gel method and functionalized with FA using EDC-NHS coupling revealed high-intensity yellow emission at 540 nm wavelength with a quantum yield of ~ 36%. In vitro viability assay at different times with 293T epithelial cells, MDA-MB-231, and T-47D cancer cells demonstrated biocompatibility and high improvement of cellular uptake by LNP functionalized with FA for cancer cells versus normal cells. Light-sheet microscopy analysis of cell-LNP interactions to visualize tagged MDA-MB-231 clusters with LNP/Ch-FA showed positive interactions due to higher stability and adherence. Biodistribution and effects on the immune system by LNP/Ch-FA nanoparticles inoculated in mice were evaluated by flow cytometer analysis. LNP/Ch-FA were well tolerated in vivo. No adverse effects were observed macroscopically. Peripheral blood analysis from animals injected with LNP/Ch-FA after 2 or 6 days of the treatment showed that a single injection of the different NPs did not have any effects on the amount of circulating neutrophils or monocytes in peripheral blood when assessed 2 or 6 days after the injection. With T cells, the core NP induced a significant decrease in circulating T cells (-31%, p=0.045) that seemed specific to the CD4+ T cells (-33%, p=0.0479). However, conjugation of the NP to chitosan prevented this effect.

Conclusions: Our work presented significant evidence that could allow a better understanding of LNPs conjugated with Ch and functionalized with FA for possible upcoming clinical applications that could work singly or in synergy with the present detection techniques to boost accuracy and precision for cancer detection without compromise the inmunosystem.

Citation Format: Rodrigo Osorio-Arciniega, Eduardo Lucero-Meza, Bonifacio Can-Uc, Israel Rocha-Mendoza, Pierrick G.J. Fournier, Gustavo A Hirata, Patricia Juarez. Chitosan luminescent rare-earth doped nanoparticles as cancer cell tracking for imaging tumors and their immune response [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4147.