Cellular fate of nanoparticles is vital to application of nanoparticles to cell imaging, bio-sensing, drug delivery, suppression of drug resistance, gene delivery, and cytotoxicity analysis. However, the current studies on cellular fate of nanoparticles have been controversial due to complications of interplay between many possible factors. By well-controlled experiments, we demonstrated unambiguously that the morphology of nanoparticles independently determined their cellular fate. We found that nanoparticles with sharp shapes, regardless of their surface chemistry, size, or composition, could pierce the membranes of endosomes that carried them into the cells and escape to the cytoplasm, which in turn significantly reduced the cellular excretion rate of the nanoparticles. Such features of sharp-shaped nanoparticles are essential for drug delivery, gene delivery, subcellular targeting, and long-term tracking. This work opens up a controllable, purely geometrical and hence safe, degree of freedom for manipulating nanoparticle-cell interaction, with numerous applications in medicine, bio-imaging, and bio-sensing.

High pressure high temperature (HPHT) nanodiamonds (NDs) represent extremely promising materials for construction of fluorescent nanoprobes and nanosensors. However, some properties of bare NDs limit their direct use in these applications: they precipitate in biological solutions, only a limited set of bio-orthogonal conjugation techniques is available and the accessible material is greatly polydisperse in shape. In this work, we encapsulate bright 30-nm fluorescent nanodiamonds (FNDs) in 10–20-nm thick translucent (i.e., not altering FND fluorescence) silica shells, yielding monodisperse near-spherical particles of mean diameter 66 nm. High yield modification of the shells with PEG chains stabilizes the particles in ionic solutions, making them applicable in biological environments. We further modify the opposite ends of PEG chains with fluorescent dyes or vectoring peptide using click chemistry. High conversion of this bio-orthogonal coupling yielded circa 2000 dye or peptide molecules on a single FND. We demonstrate the superior properties of these particles by in vitro interaction with human prostate cancer cells: while bare nanodiamonds strongly aggregate in the buffer and adsorb onto the cell membrane, the shell encapsulated NDs do not adsorb nonspecifically and they penetrate inside the cells.

A novel approach for preparation of ultra-bright fluorescent nanodiamonds (fNDs) was developed and the thermal and kinetic optimum of NV center formation was identified. Combined with a new oxidation method, this approach enabled preparation of particles that were roughly one order of magnitude brighter than particles prepared with commonly used procedures.

Core-shell nanoparticles based on fluorescent nanodiamonds coated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell were developed for background-free near-infrared imaging of cancer cells. The particles showed excellent colloidal stability in buffers and culture media. After conjugation with a cyclic RGD peptide they selectively targeted integrin αvβ3 receptors on glioblastoma cells with high internalization efficacy.