Etoposide, a DNA damage-inducing agent, is widely used for malignant tumors. However, insufficient solubility, poor bioavailability and adverse events limited the treatment outcomes and prognosis. To address this, we here developed a novel biosynthetic and unfolded protein nanocarrier to load and deliver Etoposide. Compared with the pristine agent, the loading efficiency of the nanoformulated drug increased four times and the half-life time increased to 17.6 h with controlled release of the Etoposide for 6 days. The half-maximal inhibitory concentration at 48 h was lower than that at 24 h, suggesting a long-acting anti-tumor property. Moreover, the anti-tumor performance in rat models was significantly enhanced by improving solubility and cellular internalization. Additionally, immunogenicity and adverse toxicologic effects such as kidney and liver toxicity were significantly weakened. Therefore, the assembly strategy enables etoposide with higher efficacy, bioavailability, and safety, and has great potential in the comprehensive treatment of malignant tumors.

Hollow structures have demonstrated great potential in drug delivery owing to their privileged structure, such as high surface- to-volume ratio, low density, large cavities, and hierarchical pores. In this review, we provide a comprehensive overview of hollow structured materials applied in targeting recognition, smart response, and drug release, and we have addressed the possible chemical factors and reactions in these three processes. The advantages of hollow nanostructures are summarized as follows: hollow cavity contributes to large loading capacity; a tailored structure helps controllable drug release; variable compounds adapt to flexible application; surface modification facilitates smart responsive release. Especially, because the multiple physical barriers and chemical interactions can be induced by multishells, hollow multishelled structure is considered as a promising material with unique loading and releasing properties. Finally, we conclude this review with some perspectives on the future research and development of the hollow structures as drug carriers.