targeted drug delivery and cancer theranostics. [10][11][12] However, the interaction of the solid nanocrystals with the human body on a cellular level is not well understood yet. Due to the low solubility of the employed drugs (biopharmaceutics classification system classes II and IV, solubility in water below 10 µm [13] ), lack of local mixing, and insufficient distribution volume, nanocrystals are not expected to dissolve immediately after administration, and their initial behavior rather resembles that of non-dissolving nanoparticles. [12] If not properly stealth, nanocrystals can be recognized by macrophages as foreign particles and phagocytosed, which is undesired for the intravenous nanoparticle-based formulation because it leads to fast clearance. Macrophage phagocytosis is governed by the adsorption of opsonins from the blood and thus can be minimized by surface modification with polymers repelling the proteins, such as poloxamer or polyethylene glycol (PEG). [14] This approach can be also used to minimize the macrophage uptake of nanocrystals, which is described in a related publication. [15] In the present work, we compare two types of surface modification of nanocrystals and assess their interaction with macrophages and epithelial cells. To this end, we chose two commonly used excipients-sodium dodecyl sulfate (SDS) and poloxamer 188 (P188).The biggest obstacle when studying nanocrystals made of a pure drug by standard analytical methods lies in distinguishing the solid particle from the dissolved drug form. This problem is usually faced by creating so-called hybrid nanocrystals, where a fluorescent dye is embedded into the crystal structure of the final nanocrystal. [16][17][18][19] However, such combination of multiple molecules can directly affect the drug dissolution properties and may also lead to differences in stabilizer binding.On the other hand, when using a drug molecule of unique spectral properties, for example a fluorescent drug, different strategies can be employed. To identify pure-drug nanocrystals in cells that also contain the drug in its dissolved form, we chose curcumin (CC). This naturally occurring bioactive substance from Curcuma longa is known for its wide range of biological activities that include anti-inflammatory and anticancer potential. Curcumin is fluorescent, exhibits solvatochromism, and environment-dependent fluorescence. [20][21][22] Solvatochromism is a phenomenon whereby a substance changes its spectral properties due to a solvent. Hydrogen bonding capacity and dielectric constant of a solvent directly Drug nanocrystals represent an effective way of delivering poorly water-soluble substances to target tissues and cells. Due to the large specific surface area, nanocrystals promote dissolution; therefore, the drug usually co-exists in both crystalline and dissolved forms. Commonly used analytical methods do not make it possible to easily distinguish between these forms within live cells. The present study reports a novel fluorescence microscopy method that makes it p...

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