Jain, R. K. & Stylianopoulos, T. Delivering nanomedicine to solid tumors. Nat. Rev. Clin. Oncol. 7, 653–664 (2010).

Article  CAS  Google Scholar 

Blanco, E., Shen, H. & Ferrari, M. Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33, 941–951 (2015).

Article  CAS  Google Scholar 

Huang, X. et al. Hypoxia-tropic protein nanocages for modulation of tumor- and chemotherapy-associated hypoxia. ACS Nano 13, 236–247 (2019).

Article  CAS  Google Scholar 

Dvorak, A. M. et al. The vesiculo-vacuolar organelle (VVO): a distinct endothelial cell structure that provides a transcellular pathway for macromolecular extravasation. J. Leukoc. Biol. 59, 100–115 (1996).

Article  CAS  Google Scholar 

Dvorak, A. M. & Feng, D. The vesiculo-vacuolar organelle (VVO). A new endothelial cell permeability organelle. J. Histochem. Cytochem. 49, 419–432 (2001).

Article  CAS  Google Scholar 

Claesson-Welsh, L. Vascular permeability—the essentials. Ups. J. Med Sci. 120, 135–143 (2015).

Article  Google Scholar 

Matsumura, Y. & Maeda, H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46, 6387–6392 (1986).

CAS  Google Scholar 

Sindhwani, S. et al. The entry of nanoparticles into solid tumours. Nat. Mater. 19, 566–575 (2020).

Article  CAS  Google Scholar 

Butler, K. T., Davies, D. W., Cartwright, H., Isayev, O. & Walsh, A. Machine learning for molecular and materials science. Nature 559, 547–555 (2018).

Article  CAS  Google Scholar 

Moen, E. et al. Deep learning for cellular image analysis. Nat. Methods 16, 1233–1246 (2019).

Article  CAS  Google Scholar 

Greenwald, N. F. et al. Whole-cell segmentation of tissue images with human-level performance using large-scale data annotation and deep learning. Nat. Biotechnol. 40, 555–565 (2022).

Article  CAS  Google Scholar 

Wei, Y. et al. Prediction and design of nanozymes using explainable machine learning. Adv. Mater. 34, e2201736 (2022).

Article  Google Scholar 

Lin, X. et al. Chimeric ferritin nanocages for multiple function loading and multimodal imaging. Nano Lett. 11, 814–819 (2011).

Article  CAS  Google Scholar 

Fan, K. et al. Magnetoferritin nanoparticles for targeting and visualizing tumour tissues. Nat. Nanotechnol. 7, 459–464 (2012).

Article  CAS  Google Scholar 

Litjens, G. et al. A survey on deep learning in medical image analysis. Med. Image Anal. 42, 60–88 (2017).

Article  Google Scholar 

Caicedo, J. C. et al. Data-analysis strategies for image-based cell profiling. Nat. Methods 14, 849–863 (2017).

Article  CAS  Google Scholar 

Falk, T. et al. U-Net: deep learning for cell counting, detection, and morphometry. Nat. Methods 16, 67–70 (2019).

Article  CAS  Google Scholar 

Todorov, M. I. et al. Machine learning analysis of whole mouse brain vasculature. Nat. Methods 17, 442–449 (2020).

Article  CAS  Google Scholar 

Zhang, Y. et al. Biomimetic design of mitochondria-targeted hybrid nanozymes as superoxide scavengers. Adv. Mater. 33, e2006570 (2021).

Article  Google Scholar 

Nagy, J. A., Chang, S. H., Shih, S. C., Dvorak, A. M. & Dvorak, H. F. Heterogeneity of the tumor vasculature. Semin Thromb. Hemost. 36, 321–331 (2010).

Article  CAS  Google Scholar 

Feng, D., Nagy, J. A., Dvorak, A. M. & Dvorak, H. F. Different pathways of macromolecule extravasation from hyperpermeable tumor vessels. Microvasc. Res. 59, 24–37 (2000).

Article  CAS  Google Scholar 

Bonam, S. R., Wang, F. & Muller, S. Lysosomes as a therapeutic target. Nat. Rev. Drug Discov. 18, 923–948 (2019).

Article  CAS  Google Scholar 

Rennick, J. J., Johnston, A. P. R. & Parton, R. G. Key principles and methods for studying the endocytosis of biological and nanoparticle therapeutics. Nat. Nanotechnol. 16, 266–276 (2021).

Article  CAS  Google Scholar 

Tai, W., Li, J., Corey, E. & Gao, X. A ribonucleoprotein octamer for targeted siRNA delivery. Nat. Biomed. Eng. 2, 326–337 (2018).

Article  CAS  Google Scholar 

Bern, M. et al. An engineered human albumin enhances half-life and transmucosal delivery when fused to protein-based biologics. Sci. Transl. Med. 12, eabb0580 (2020).

Article  CAS  Google Scholar 

Yokota, S. & Fahimi, H. D. Immunocytochemical localization of albumin in the secretory apparatus of rat liver parenchymal cells. Proc. Natl Acad. Sci. USA 78, 4970–4974 (1981).

Article  CAS  Google Scholar 

Shroyer, K. R. & Nakane, P. K. Immunohistochemical localization of albumin and in situ hybridization of albumin mRNA. Cell Biochem. Funct. 5, 195–210 (1987).

Article  CAS  Google Scholar 

Pelletier, L., Jokitalo, E. & Warren, G. The effect of Golgi depletion on exocytic transport. Nat. Cell Biol. 2, 840–846 (2000).

Article  CAS  Google Scholar 

De Matteis, M. A. & Luini, A. Exiting the Golgi complex. Nat. Rev. Mol. Cell Biol. 9, 273–284 (2008).

Article  Google Scholar 

Jiang, B. et al. A natural drug entry channel in the ferritin nanocage. Nano Today 35, 100948 (2020).

Article  CAS  Google Scholar 

Huang, X. et al. Protein nanocages that penetrate airway mucus and tumor tissue. Proc. Natl Acad. Sci. USA 114, E6595–E6602 (2017).

Article  CAS  Google Scholar 

Liu, Q. et al. Modular assembly of tumor-penetrating and oligomeric nanozyme based on intrinsically self-assembling protein nanocages. Adv. Mater. 33, e2103128 (2021).

Article  Google Scholar 

Ronneberger, O., Fischer, P. & Brox, T. U-Net: convolutional networks for biomedical image segmentation. Med. Image Comput. Comput. Assist. Interv. 9351, 234–241 (2015).

Google Scholar