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Self-assembled materials capable of modulating their assembly properties in response to specific enzymes play a pivotal role in advancing ‘intelligent’ encapsulation platforms for biotechnological applications. Here, we introduce a previously unreported class of synthetic nanomaterials that programmatically interact with histone deacetylase (HDAC) as the triggering stimulus for disassembly. These nanomaterials consist of co-polypeptides comprising poly (acetyl L-lysine) and poly(ethylene glycol) blocks. Under neutral pH conditions, they self-assemble into particles. However, their stability is compromised upon exposure to HDACs, depending on enzyme concentration and exposure time. Our investigation, utilizing HDAC8 as the model enzyme, revealed that the primary mechanism behind disassembly involves a decrease in amphiphilicity within the block copolymer due to the deacetylation of lysine residues within the particles’ hydrophobic domains. To elucidate the response mechanism, we encapsulated a fluorescent dye within these nanoparticles. Upon incubation with HDAC, the nanoparticle structure collapsed, leading to controlled release of the dye over time. Notably, this release was not triggered by denatured HDAC8, other proteolytic enzymes like trypsin, or the co-presence of HDAC8 and its inhibitor. We further demonstrated the biocompatibility and cellular effects of these materials and conducted a comprehensive computational study to unveil the possible interaction mechanism between enzymes and particles. By drawing parallels to the mechanism of naturally occurring histone proteins, this research represents a pioneering step toward developing functional materials capable of harnessing the activity of epigenetic enzymes such as HDACs. 

We propose a new measurement of the ratio of positron-proton to electron-proton elastic scattering at DESY. The purpose is to determine the contributions beyond single-photon exchange, which are essential for the Quantum Electrodynamic (QED) description of the most fundamental process in hadronic physics. By utilizing a 20 cm long liquid hydrogen target in conjunction with the extracted beam from the DESY synchrotron, we can achieve an average luminosity of$$2.12\times 10^{35}$$$2.12\times {10}^{35}$ cm$$^{-2}\cdot $$${}^{-2}·$s$$^{-1}$$${}^{-1}$ ($$\approx 200$$$\approx 200$times the luminosity achieved by OLYMPUS). The proposed two-photon exchange experiment (TPEX) entails a commissioning run at a beam energy of 2 GeV, followed by measurements at 3 GeV, thereby providing new data up to$$Q^2=4.6$$$Q^2=4.6$ (GeV/c)$$^2$$${}^2$(twice the range of current measurements). We present and discuss the proposed experimental setup, run plan, and expectations.