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The delivery of various drug molecules into cells is crucial in modern medicine.[1, 2] Most naked biomolecules and some free drugs are poorly delivered to cells owing to poor stability, low solubility and/or unwanted toxicity. For these reasons, various natural and synthetic vectors have been used as cellular delivery vehicles. Compared to viral vectors having high delivery efficiency,[3, 4] non-viral vectors such as nanoparticles are safer delivery tools,[5] but their cellular delivery efficiency is far from satisfactory.[6] It remains an ongoing challenge to develop nonviral carrier systems having both good safety and high delivery efficiency.

The understanding of structure–function relationships in natural systems, such as enveloped viruses, provides a useful guide for the design of new nanocarriers. Enveloped viruses have sizes around 30–400 nm, which appears to be ideal for cellular uptake.[7] Their high infectivity is mainly attributed to receptor-specific interactions, facilitating subsequent viral fusion or cellular uptake.[3, 8] This concept has been used in the design of nanocarriers.[9] Recent developments in state-of-theart electron tomography (ET) have provided “nano-ecology” information for many enveloped viruses, for example, influenza virus,[8] herpes simplex virus (HSV),[10] and human immunodeficiency virus (HIV),[11] all showing rough surfaces patched by glycoprotein spikes. However, the influence of nanoscale surface roughness on cellular delivery efficiency remains unclear because it is always associated with receptor–ligand specific interactions in viral systems.