Long-Term Cell-Membrane-Coated Ultrabright Nanospheres for Targeted Cancer Cell Imaging and Hydrophobic Drug Delivery

Abstract

Nanoparticle-based imaging agents have gained massive attention for the targeted cancer cell imaging of early stage disease diagnosis. Among these, organic dye-entrapped and -assembled nanoparticles have been considered as potential imaging agents. However, they are limited by poor brightness, low stability, low reproducibility, and selective surface engineering, which limit their translational potential. The molecular assembly of amphiphilic precursors and the chosen organic fluorophore can augment the brightness and stability of the engineered nanoimaging agents. Herein, we describe cancer cell-membrane-covered ICG-cellulose acetate nanospheres (180 nm) as biomimetic ultrabright nanoimaging agents for cancer cell imaging. Engineered biomimetic ultrabright imaging agents are compared with folic-acid-conjugated ultrabright nanospheres. Encapsulation of fluorescent organic molecules (660 dye molecules/per nanoparticle) in the core of a polymeric network enhances the overall brightness and long-term photostability due to the unique assembly of the loaded fluorescent cargo and poor permeation of oxygen to oxidize the dye. The amphiphilic nature of the selected polymeric network accommodates both hydrophilic and hydrophobic cargo molecules (e.g., imaging and therapeutics). The engineered fluorescent nanoparticles exhibit high brightness, uniform particle size distribution, high stability, good biocompatibility with normal cells, and high scalability. For targeted chemotherapeutics, DOX-loaded biomimetic nanospheres demonstrate better chemotherapeutic response (more than 95% cancer cell death) than folic acid-attached DOX-loaded nanoparticles (78% cancer cell death). The engineered nanospheres exhibited cancer cell imaging and therapeutics capabilities by delivering imaging and drug molecules in cancer-mimicked environment in vitro. Our findings suggest that the engineered ultrabright nanospheres not only overcome the limitations of nanoimaging but also provide additional advantages for targeted cancer therapeutics. © 2025 American Chemical Society.