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.

] Department of Physics and Centre for Quantum Coherence The Chinese University of Hong Kong Shatin New Territories Hong Kong [2] The Chinese University of Hong Kong ShenZhen Research Institute ShenZhen China

Department of Physics and Centre for Quantum Coherence The Chinese University of Hong Kong Shatin New Territories Hong Kong

Institute of Atomic and Molecular Sciences Academia Sinica Taipei 106 Taiwan

Laboratory of Synthetic Nanochemistry Institute of Organic Chemistry and Biochemistry AS CR v v i Flemingovo nam 2 166 10 Prague 6 Czech Republic

School of Biomedical Sciences Faculty of medicine The Chinese University of Hong Kong Shatin New Territories Hong Kong

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