Mesoporous nanoperforators as membranolytic agents via nano- and molecular-scale multi-patterning.

Plasma membrane lysis is an effective anticancer strategy, which mostly relying on soluble molecular membranolytic agents. However, nanomaterial-based membranolytic agents has been largely unexplored. Herein, we introduce a mesoporous membranolytic nanoperforators (MLNPs) via a nano- and molecular-scale multi-patterning strategy, featuring a spiky surface topography (nanoscale patterning) and molecular-level periodicity in the spikes with a benzene-bridged organosilica composition (molecular-scale patterning), which cooperatively endow an intrinsic membranolytic activity. Computational modelling reveals a nanospike-mediated multivalent perforation behaviour, i.e., multiple spikes induce nonlinearly enlarged membrane pores compared to a single spike, and that benzene groups aligned parallelly to a phospholipid molecule show considerably higher binding energy than other alignments, underpinning the importance of molecular ordering in phospholipid extraction for membranolysis. Finally, the antitumour activity of MLNPs is demonstrated in female Balb/c mouse models. This work demonstrates assembly of organosilica based bioactive nanostructures, enabling new understandings on nano-/molecular patterns co-governed nano-bio interaction.

Engineering Crystallinity Gradients for Tailored CaO2 Nanostructures: Enabling Alkalinity-Reinforced Anticancer Activity with Minimized Ca2+/H2O2 Production.

CaO2 nanoparticles (CNPs) can produce toxic Ca2+ and H2O2 under acidic pH, which accounts for their intrinsic anticancer activity but at the same time raises safety concerns upon systemic exposure. Simultaneously realizing minimized Ca2+/H2O2 production and enhanced anticancer activity poses a dilemma. Herein, we introduce a "crystallinity gradient-based selective etching" (CGSE) strategy, which is realized by creating a crystallinity gradient in a CNP formed by self-assembled nanocrystals. The nanocrystals distributed in the outer layer have a higher crystallinity and thus are chemically more robust than those distributed in the inner layer, which can be selectively etched. CGSE not only leads to CNPs with tailored single- and double-shell hollow structures and metal-doped compositions but more surprisingly enables significantly enhanced anticancer activity as well as tumor growth inhibition under limited Ca2+/H2O2 production, which is attributed to an alkalinity-reinforced lysosome-dependent cell death pathway.

Synthesis of dendritic mesoporous organosilica nanoparticles under a mild acidic condition with homogeneous wall structure and near-neutral surface.

Dendritic mesoporous organosilica nanoparticles were synthesized under a mild acidic condition (pH 6.2), featuring a molecularly homogeneous wall structure and an unusual near-neutral charged surface, consequently enabling reduced protein fouling property.

Surfactant-free synthesis of monodispersed organosilica particles with pure sulfide-bridged silsesquioxane framework chemistry via extension of Stöber method.

Sulfide bond incorporated organosilica particles have been broadly applied to versatile biomedical applications, wherein the uniformity of particles and the sulfur content significantly dictate the ultimate performance. Unfortunately, due to the difficulty in controlling the chemical behavior of organosilica precursors in a sol-gel process, challenges still exist in developing a facile and green synthetic approach to fabricate organosilica particles with good dispersity and high sulfur content. In the present work, by extending the classic Stöber method, a surfactant-free synthesis of monodispersed organosilica particles with pure sulfide-bridged silsesquioxane framework chemistry is reported for the first time. By simply tailoring the ethanol-to-water ratio and amount of catalyst, the size of disulfide-bridged organosilica particles can be tuned from ~0.50 to ~1.20 µm. Moreover, this approach can be employed to prepare tetra-sulfide bridged silica nanoparticles with an extremely high sulfur content of 30.7 wt% and negligible cytotoxicity. Notably, taking advantage of this extended Stöber method, both hydrophilic (methylene blue) and hydrophobic (curcumin) molecules can be in-situ encapsulated into tetra-sulfide bridged silica nanoparticles, whose glutathione-triggered biodegradability is also demonstrated. Collectively, the innovative synthetic approach and organosilica particles developed in this work are expected to open up new opportunities in hybrid materials fabrication and bio-applications.

Lyophilization enabled disentanglement of polyethylenimine on rambutan-like silica nanoparticles for enhanced plasmid DNA delivery.

Polyethylenimine (PEI) functionalization onto nanoparticles is a widely used strategy for constructing particulate vectors for gene delivery. However, how to control the conformation of PEI chains and the resultant impact on gene transfection efficiency remains largely unexplored. Herein, we report that drying methods dramatically affect the conformation of PEI chains modified on the surface of silica nanoparticles and consequently the plasmid DNA transfection performance. Specifically, lyophilization renders less entangled PEI compared to commonly used vacuum drying as evidenced by an elevated glass transition temperature. The lyophilization induced disentangled conformation is likely associated with the solid-to-gas phase transition drying mechanism, which removes the bound crystal water content and thus reduces hydrogen bonding between amines. Moreover, we find that the stretched PEI chains on the surface of rambutan-like silica nanoparticles promote their binding capacity towards plasmid DNA molecules and thereby enhanced gene delivery and transfection efficiency. Our findings have provided new understanding about amine based polymers modified on nanoparticles, and have significant implications on the design of efficient particulate vectors for gene delivery.