Programmable Recruitment of Mesoporous Silica Nanoparticles for Engineering Hard–Soft Interfaces in DNA Condensates

Mesoporous silica nanoparticles (MSNPs) are a versatile class of biocompatible nanomaterials with well-defined and tunable physicochemical properties, including controllable r, high surface area, and facile surface functionalization, which enable their widespread use in complex biological and biomimetic systems1,2. These features make MSNPs particularly attractive as a multifunctional platform for incorporation into soft materials to create hybrid structures with unique dynamic properties. In this work, we asked whether MSNPs could be incorporated as client components within liquid-liquid phase separation (LLPS) DNA condensates, an emerging class of programmable soft materials capable of mimicking key features of biomolecular condensates. Previous studies have shown that LLPS DNA condensates can interact with small molecules3, proteins,4 and particles5; however, the possibility to spatially confine hard silica nanoparticles within them remains largely unexplored. To address this question, we constructed a toolbox of fluorescent MSNPs with embedded rhodamine, spanning a broad size range (approximately 90, 150, and 700 nm) and distinct surface chemistries (carboxylated and DBCO-modified). Their integration into DNA condensates was achieved by anchoring single-stranded DNA onto the particle surface, with the complementary sequence included in a DNA nanostar condensate design. DNA nanostars undergo liquid–liquid phase separation and enable the formation of dynamic, micron-sized condensates with tunable structural properties. The presence of the complementary anchoring strand enabled direct interactions with the condensate, allowing the incorporation of nanoparticles with both surface chemistries without a strict size cutoff, whereas in the absence of the strand the particles remained excluded. Current results demonstrate that MSNPs recruitment and spatial organization within the condensates are highly controllable through nanoparticle size, surface chemistry, and sequence-specific DNA hybridization. Confocal microscopy and 3D reconstructions show homogeneous particle dispersion across the condensate volume, while kinetic and coalescence experiments reveal that incorporated SiNPs modulate condensate growth, fusion, and viscoelastic behavior. These results establish a well-defined hybrid material platform in which structural organization and material properties are governed by programmable nucleic-acid interactions, offering new opportunities for the design of dynamic and programmable interfaces. References: (1) Wu, S.-H.; Hung, Y.; Mou, C.-Y. Chem. Commun. 2011, 47 (36), 9972. (2) Manzano, M.; Vallet‐Regí, M. Adv. Funct. Mater. 2020, 30 (2), 1902634. (3) Ambadi Thody, S.; Clements, H. D.; Baniasadi, H.; Lyon, A. S.; Sigman, M. S.; Rosen, M. K. Nat. Chem. 2024, 16 (11), 1794–1802. (4) Dizani, M.; Sorrentino, D.; Agarwal, S.; Stewart, J.M.; Franco, E. J. Am. Chem. Soc. 2024, 146, 29344–29354 (5) Kelley, F. M.; Ani, A.; Pinlac, E. G.; Linders, B.; Favetta, B.; Barai, M.; Ma, Y.; Singh, A.; Dignon, G. L.; Gu, Y.; Schuster, B. Nat. Commun. 2025, 16, 3521.