Dual-imaging nanoparticles based on surface-modified magnetic nanoparticles and biodegradable photoluminescent polymers

Nikhil Pandey ^1* Priyanka Iyer ¹ Tejaswi D Kadapure ¹ Jian Yang ² Kytai Truong Nguyen ¹ Aniket S Wadajkar ^1*

• ¹ Department of Bioengineering, College of Engineering, University of Texas at Arlington, Arlington, Texas, United States
• ² Department of Biomedical Engineering, The Pennsylvania State University, University Park, United States

Theranostic nanoparticles have gained increasing interest in disease management over the past decade due to their combined diagnostic and therapeutic capabilities. We had previously developed dual-imaging enabled cancer-targeting nanoparticles (DICT-NPs) based on the combination of a biodegradable photoluminescent polymer (BPLP) and iron oxide-based superparamagnetic nanoparticles (MNPs). DICT-NPs showed cyto-compatibility, magnetic targeting, and imaging capabilities, but their inconsistent fluorescence was due to the MNP core's quenching and inefficient BPLP grafting. To address these limitations, we investigated the effects of modifying the MNP surface with silane, hydroxyapatite, or silane-coupled azide coatings before BPLP conjugation, and evaluated the impact on the fluorescence properties of the resulting surfacemodified DICT-NPs (mDICT-NPs). mDICT-NPs were 200-350 nm in diameter and cytocompatible with human dermal fibroblasts as well as normal human prostate epithelial cells. Surface modifications of MNPs and conjugation with BPLP did not alter the superparamagnetic properties, but improved nanoparticle fluorescence output by ~50% compared to previously developed DICT-NPs. Hydroxyapatite-modified DICT-NPs showed the most noteworthy improvements including: (1) a sustained release of Paclitaxel or Docetaxel, 71% and 68% over a 21 day period, respectively, (2) dose-dependent tumor cell uptake in melanoma, thyroid and prostate cancer cells with the highest uptake of over 60% at 500 µg/mL, and (3) a reduction in cancer cell viability with less than 50% viability in the TT thyroid cancer cell and KAT-4 cancer cell lines. The development of mDICT-NPs represents a crucial advancement in overcoming challenges of fluorescence quenching associated with iron oxide-based magneto-fluorescent theranostic nanoparticle platforms.