Fig. 1. Schematic illustration of the design of eTuSp1 and the application of eTuSp1 spheres in lysosomal delivery systems. (A) Engineered spider-eggcase-silk proteins from a black widow spider. In comparison to bare proteins, the isoelectric point of recombinant proteins can be flexibly regulated from 3.35 to 5.56 by fusing with different numbers of His Tags. (B) Fabrication process of eTuSp1 spheres by the HFIP-on-oil method. (C) The pI-mediated drug loading and release of eTuSp1-Dox spheres. Silk spheres are loaded with Dox (red) in the negative (green) state and release the drug in the positive (purple) state. (D) Internalization and intracellular drug release. (1) Endocytosis; (2) trafficking; (3) drug release.