In vitro protein folding is a complex process which often results in protein aggregation, low yields and low speci�c activity. We report the use of nanoscale exoshells (tES) to provide speci�c nanoenvironments for the folding and release of 12 highly diverse protein substrates ranging from small protein toxins to human albumin, a dimeric protein (alkaline phosphatase), a trimeric ion channel (Omp2a) and the tetrameric tumor suppressor, p53. These proteins represent a unique diversity in size, volume, disul�de linkages, isoelectric point and multi versus monomeric nature of their functional units. Crude soluble yield (3-fold to > 100-fold), functional yield (2-fold to > 100-fold) and speci�c activity (3-fold to > 100-fold) were increased for all the proteins tested. The average soluble yield of POI was 6.5 mg/100 mg of tES. Charge complementation between the tES internal cavity and the protein substrate was the primary determinant in functional folding. Our results con�rm the importance of nanoscale electrostatic effects and provide a novel nanoparticle solution for folding proteins in vitro. energetics. Three tES-F116H charge self according to their charge (labelled next to the ordinate) and stabilizing effect. f, Low molecular weight proteins require high molar ratios to stabilize the assembly. Thermal denaturation temperatures of tES-F116H were measured via DFS as the concentation of POI is titrated against tES-F116H during the loading phase of the folding protocol. g, tES-F116H undergo pH mediated assembly and disassembly. Shell diameter can be monitored using DLS (lower panel) and no signi�cant soluble protein loss is observed after 10 cycles (upper panel). Titration of POI results in shifts of tES-F116H mass consistent with the steric limits of the tES interior (~80 kDa).