Cecília Leal

Here we demonstrate materials and operating conditions that allow for high-resolution printing of layers of quantum dots (QDs) with precise control over thickness and submicron lateral resolution and capabilities for use as active layers of QD light-emitting diodes (LEDs). The shapes and thicknesses of the QD patterns exhibit systematic dependence on the dimensions of the printing nozzle and the ink composition in ways that allow nearly arbitrary, systematic control when exploited in a fully automated printing tool. Homogeneous arrays of patterns of QDs serve as the basis for corresponding arrays of QD LEDs that exhibit excellent performance. Sequential printing of different types of QDs in a multilayer stack or in an interdigitated geometry provides strategies for continuous tuning of the effective, overall emission wavelengths of the resulting QD LEDs. This strategy is useful to efficient, additive use of QDs for wide ranging types of electronic and optoelectronic devices.

RNA therapeutics have the potential to resolve a myriad of genetic diseases. Lipid nanoparticles (LNPs) are among the most successful RNA delivery systems. Expanding their use for the treatment of more genetic diseases hinges on our ability to continuously evolve the design of LNPs with high potency, cellular-specific targeting, and low side effects. Overcoming the difficulty of releasing cargo from endocytosed LNPs remains a significant hurdle. Here, we investigate the fundamental properties of nonviral RNA nanoparticles pertaining to the activation of topological transformations of endosomal membranes and RNA translocation into the cytosol. We show that, beyond composition, LNP fusogenicity can be prescribed by designing LNP nanostructures that lower the energetic cost of fusion and fusion–pore formation with a target membrane. The inclusion of structurally active lipids leads to enhanced LNP endosomal fusion, fast evasion of endosomal entrapment, and efficacious RNA delivery. For example, conserving the lipid make-up, RNA–LNPs having cuboplex nanostructures are significantly more efficacious at endosomal escape than traditional lipoplex constructs.

RNA interference (RNAi) is an evolutionarily conserved sequence-specific post-transcriptional gene silencing pathway with wide-ranging applications in functional genomics, therapeutics, and biotechnology. Cationic liposome-small interfering RNA (CL-siRNA) complexes have emerged as vectors of choice for delivery of siRNA, which mediates RNAi. However, siRNA delivery by CL-siRNA complexes is often inefficient and accompanied by lipid toxicity. We report the development of CL-siRNA complexes with a novel cubic phase nanostructure, which exhibit efficient silencing at low toxicity. The inverse bicontinuous gyroid cubic nanostructure was unequivocally established from synchrotron X-ray scattering data, while fluorescence microscopy revealed colocalization of lipid and siRNA in complexes. We attribute the efficient silencing to enhanced fusion of complex and endosomal membranes, facilitated by the cubic phase membrane's positive Gaussian modulus, which may enable spontaneous formation of transient pores. The findings underscore the importance of understanding membrane-mediated interactions between CL-siRNA complex nanostructure and cell components in developing CL-based gene silencing vectors.

Materials that can be switched between low and high thermal conductivity states would advance the control and conversion of thermal energy. Employing in situ time-domain thermoreflectance (TDTR) and in situ synchrotron X-ray scattering, we report a reversible, light-responsive azobenzene polymer that switches between high (0.35 W m −1 K −1 ) and low thermal conductivity (0.10 W m −1 K −1 ) states. This threefold change in the thermal conductivity is achieved by modulation of chain alignment resulted from the conformational transition between planar ( trans ) and nonplanar ( cis ) azobenzene groups under UV and green light illumination. This conformational transition leads to changes in the π-π stacking geometry and drives the crystal-to-liquid transition, which is fully reversible and occurs on a time scale of tens of seconds at room temperature. This result demonstrates an effective control of the thermophysical properties of polymers by modulating interchain π-π networks by light.

RNAi technology is currently experiencing a revival due to remarkable improvements in efficacy and viability through oligonucleotide chemical manipulations and/or via their packaging into nanoscale carriers. At present, there is no FDA-approved system for siRNA technology in humans. The design of the next generation of siRNA carriers requires a deep understanding of how a nanoparticle's physicochemical properties truly impart biological stability and efficiency. For example, we now know that nanoparticles need to be sterically stabilized in order to meet adequate biodistribution profiles. At present, targeting, uptake, and, in particular, endosomal escape are among the most critical challenges impairing RNAi technologies. The disruption of endosomes encompasses membrane transformations (for example, pore formation) that cost significant elastic energy. Nanoparticle size and shape have been identified as relevant parameters impacting tissue accumulation and cellular uptake. In this paper, we demonstrate that the internal structure of lipid-based particles offers a different handle to promote endosomal membrane topological disruptions that enhance siRNA delivery. Specifically, we designed sterically stabilized lipid-based particles that differ from traditional liposomal systems by displaying highly ordered bicontinuous cubic internal structures that can be loaded with large amounts of siRNA. This system differs from traditional siRNA-containing liposomes (lipoplexes) as the particle-endosomal membrane interactions are controlled by elasticity energetics and not by electrostatics. The resulting "PEGylated cuboplex" has the ability to deliver siRNA and specifically knockdown genes with efficiencies that surpass those achieved by traditional lipoplex systems.