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Nanoparticle-based imaging agents have gained massive attention for the targeted imaging of early-stage cancer. Among these, organic dye-entrapped/assembled nanoparticles have been recognized as potential imaging agents. However, they are limited by poor brightness, low stability, low reproducibil-ity and scalability, and selective surface engineering, which limits their translational potential. The mo-lecular assembly of amphiphilic precursor molecules and the chosen fluorophore can augment the brightness and stability of engineered nanoimaging agents. Herein, we describe an original engineering method for cancer cell membrane-covered ICG-cellulose acetate nanospheres (180 nm) as biomimetic ultra-bright nanoimaging agents for cancer cell imaging. The targeted cancer cell imaging is compared with folic acid-attached ICG-cellulose acetate nanospheres. Encapsulation of fluorescent organic mole-cules (660 dye molecules/ per nanoparticle) in the core of a polymeric network enhances the overall brightness and long-term photostability due to the entrapment 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 exhibited high brightness (780-980 MESF), uniform particle size distribution (180-240 nm), high stability (tested up to 90 days), good biocompatibility with normal cells (95 %), and high scalability (600 mL/batch). For targeted chemotherapeutics, DOX-loaded bio-mimetic nanoparticles demonstrate better chemotherapeutic response (more than 95 % cancer cell death) than folic acid-attached DOX-loaded nanoparticles (78 % cancer cell death) as identified with 24 h MTT assay. The engineered nanoparticles exhibited cancer cell imaging and therapeutics capabili-ties by delivering imaging and drug molecules in cancer mimicked environment in vitro. Our findings suggest that the engineered nanoparticles not only overcome the limitations of nano-imaging but also provide additional advantages for targeted cancer therapeutics. 

Here we address an important roadblock that prevents the use of bright fluorescent nanoparticles as individual ratiometric sensors: the possible variation of fluorescence spectra between individual nanoparticles. Ratiometric measurements using florescent dyes have shown their utility in measuring the spatial distribution of temperature, acidity, and concentration of various ions. However, the dyes have a serious limitation in their use as sensors; namely, their fluorescent spectra can change due to interactions with the surrounding dye. Encapsulation of the d, e in a porous material can solve this issue. Recently, we demonstrated the use of ultrabright nanoporous silica nanoparticles (UNSNP) to measure temperature and acidity. The particles have at least two kinds of encapsulated dyes. Ultrahigh brightness of the particles allows measuring of the signal of interest at the single particle level. However, it raises the problem of spectral variation between particles, which is impossible to control at the nanoscale. Here, we study spectral variations between the UNSNP which have two different encapsulated dyes: rhodamine R6G and RB. The dyes can be used to measure temperature. We synthesized these particles using three different ratios of the dyes. We measured the spectra of individual nanoparticles and compared them with simulations. We observed a rather small variation of fluorescence spectra between individual UNSNP, and the spectra were in very good agreement with the results of our simulations. Thus, one can conclude that individual UNSNP can be used as effective ratiometric sensors.