Combination of Backbone Rigidity and Richness in Aryl Structures Enables Direct Membrane Translocation of Polymer Scaffolds for Efficient Gene Delivery.

The development of cell-penetrating polymers with endocytosis-independent cell uptake pathways has emerged as a prominent strategy to enhance the transfection efficiency. Inspired by the rigid α-helical structure that endows polypeptides with cell-penetrating ability, we propose that a rigid backbone can facilitate the corresponding polymer vector's performance in gene delivery by bypassing the difficult endosomal escape process. Meanwhile, the installation of aromatic domains, as a way to promote gene transfection efficiency, is employed through the construction of a poly(benzyl ether) (PBE)-based scaffold in this work. We demonstrate that the direct membrane translocation capability of the synthesized PBE contributes to its enhanced transfection performance and excellent biocompatibility profile, rendering the imidazolium-functionalized PBE scaffold with higher activity and biocompatibility. Molecular details of the PBE-lipid interaction are also revealed in molecular dynamics simulations, indicating the important roles of individual structural elements on the polymeric scaffold in the membrane penetration process.

Molecular spherical nucleic acids.

Herein, we report a class of molecular spherical nucleic acid (SNA) nanostructures. These nano-sized single molecules are synthesized from T8 polyoctahedral silsesquioxane and buckminsterfullerene C60 scaffolds, modified with 8 and 12 pendant DNA strands, respectively. These conjugates have different DNA surface densities and thus exhibit different levels of nuclease resistance, cellular uptake, and gene regulation capabilities; the properties displayed by the C60 SNA conjugate are closer to those of conventional and prototypical gold nanoparticle SNAs. Importantly, the C60 SNA can serve as a single entity (no transfection agent required) antisense agent to efficiently regulate gene expression. The realization of molecularly pure forms of SNAs will open the door for studying the interactions of such structures with ligands and living cells with a much greater degree of control than the conventional polydisperse forms of SNAs.

Well-Defined DNA-Polymer Miktoarm Stars for Enzyme-Resistant Nanoflares and Carrier-Free Gene Regulation.

Herein, we report a star-architectured poly(ethylene glycol) (PEG)-oligonucleotide nanoconjugate of a well-defined molecular structure. Based upon fullerene C60 cores, each star bears precisely 1 DNA strand and 11 polymer chains. The elevated PEG density provides the DNA with steric selectivity: the DNA is significantly more resistant to nuclease digestion while remaining able to hybridize with a complementary sequence. The degree of resistance increases as the centers of mass for the DNA and fullerene are closer together. Such steric selectivity reduces protein-related background signals of the nanoflares synthesized from these miktoarm star polymers. Importantly, the stars improve cellular uptake and regulate gene expression as a non-cytotoxic, single-entity antisense agent without the need for a transfection carrier.

A nanoscale MOF-based heterogeneous catalytic system for the polymerization of N-carboxyanhydrides enables direct routes toward both polypeptides and related hybrid materials.

Synthetic polypeptides have emerged as versatile tools in both materials science and biomedical engineering due to their tunable properties and biodegradability. While the advancements of N-carboxyanhydride (NCA) ring-opening polymerization (ROP) techniques have aimed to expedite polymerization and reduce environment sensitivity, the broader implications of such methods remain underexplored, and the integration of ROP products with other materials remains a challenge. Here, we show an approach inspired by the success of many heterogeneous catalysts, using nanoscale metal-organic frameworks (MOFs) as co-catalysts for NCA-ROP accelerated also by peptide helices in proximity. This heterogeneous approach offers multiple advantages, including fast kinetics, low environment sensitivity, catalyst recyclability, and seamless integration with hybrid materials preparation. The catalytic system not only streamlines the preparation of polypeptides and polypeptide-coated MOF complexes (MOF@polypeptide hybrids) but also preserves and enhances their homogeneity, processibility, and overall functionalities inherited from the constituting MOFs and polypeptides.

Novel Organic Superbase Dopants for Ultraefficient N-Doping of Organic Semiconductors.

Doping is a powerful technique for engineering the electrical properties of organic semiconductors (OSCs), yet efficient n-doping of OSCs remains a central challenge. Herein, the discovery of two organic superbase dopants, namely P2-t-Bu and P4-t-Bu as ultra-efficient n-dopants for OSCs is reported. Typical n-type semiconductors such as N2200 and PC61 BM are shown to experience a significant increase of conductivity upon doping by the two dopants. In particular, the optimized electrical conductivity of P2-t-Bu-doped PC61 BM reaches a record-high value of 2.64 S cm-1 . The polaron generation efficiency of P2-t-Bu-doped in PC61 BM is found to be over 35%, which is 2-3 times higher than that of benchmark n-dopant N-DMBI. In addition, a deprotonation-initiated, nucleophilic-attack-based n-doping mechanism is proposed for the organic superbases, which involves the deprotonation of OSC molecules, the nucleophilic attack of the resulting carbanions on the OSC's π-bonds, and the subsequent n-doping through single electron transfer process between the anionized and neutral OSCs. This work highlights organic superbases as promising n-dopants for OSCs and opens up opportunities to explore and develop highly efficient n-dopants.

Molecularly pure miktoarm spherical nucleic acids: preparation and usage as a scaffold for abiotic intracellular catalysis.

We present a fullerene-based strategy that allows the synthesis of molecularly pure miktoarm spherical nucleic acids (SNAs) with diverse structures, which, with post-functionalization, could serve as efficient scaffolds for intracellular catalysis. The SNA structure promotes cell permeability, nucleic acid stability, and catalytic efficiency, making the platform ideal for in cellulo reactions. Consequently, the tris(triazole)-bearing miktoarm SNA was able to effectively mediate intracellular copper-catalyzed alkyne-azide cycloaddition at nanomolar level of copper, and facilitate the same reaction in live zebrafish.

Functionalizable, Side Chain-Immolative Poly(benzyl ether)s.

Herein, we report a poly(benzyl ether)-based self-immolative polymer (SIP) with pendant pyridine disulfide groups. Cleavage of the side-chain disulfides leads to the formation of phenolates, which initiate depolymerization from the side chain. Due to the higher density of the disulfide groups compared to that of the chain-end-capping group, which normally is responsible for initiating depolymerization of SIPs, the side chain-immolative polymer (ScIP) can be readily degraded in the solid state where the mobility of polymer chains is substantially limited. The ScIP was also further modified through the thiol-disulfide exchange reaction to prepare ScIP-g-poly(ethylene glycol) graft polymers and organogels, which were also able to undergo complete reductive self-immolative degradation.

Modulating the Depolymerization of Self-Immolative Brush Polymers with Poly(benzyl ether) Backbones.

We have synthesized a series of stimuli-responsive brush polymers by grafting azide-terminated side chains onto a self-immolative, alkyne-bearing poly(benzyl ether) backbone, which is prepared by anionic polymerization of quinone methide-based monomers. Upon exposure to a decapping reagent (Pd(0) or F-), these brush polymers undergo an irreversible degradation cascade from head to tail to yield individual side chains. It is observed that several factors affect the depolymerization kinetics, including solvent polarity, type of counterion, the rate of the decapping chemistry, and interestingly, the rigidity of the side chains.

Facile fabrication of magnetic carboxymethyl starch/poly(vinyl alcohol) composite gel for methylene blue removal.

This study presents a simple method to fabricate magnetic carboxymethyl starch/poly(vinyl alcohol) (mCMS/PVA) composite gel. The obtained mCMS/PVA was characterized by Fourier transform infrared (FTIR) spectra, vibrating-sample magnetometer (VSM) and scanning electron microscopy (SEM) measurements. The application of mCMS/PVA as an adsorbent for removal of cationic methylene blue (MB) dye from water was investigated. Benefiting from the combined merits of carboxymethyl starch and magnetic gel, the mCMS/PVA simultaneously exhibited excellent adsorption property toward MB and convenient magnetic separation capability. The effects of initial dye concentration, contact time, pH and ionic strength on the adsorption performance of mCMS/PVA adsorbent were investigated systematically. The adsorption process of mCMS/PVA for MB fitted pseudo-second-order model and Freundlich isotherm. Moreover, desorption experiments revealed that the mCMS/PVA adsorbent could be well regenerated in ethanol solution without obvious compromise of removal efficiency even after eight cycles of desorption/adsorption. Considering the facile fabrication process and robust adsorption performance, the mCMS/PVA composite gel has great potential as a low cost adsorbent for environmental decontamination.

Multihydroxy dendritic upconversion nanoparticles with enhanced water dispersibility and surface functionality for bioimaging.

Upconversion nanoparticle (UCNP) as a new class of imaging agent is gaining prominence because of its unique optical properties. An ideal UCNP for bioimaging should simultaneously possess fine water dispersibility and favorable functional groups. In this paper, we present a simple but effective method to the synthesis of a UCNP-based nanohybrid bearing a multihydroxy hyperbranched polyglycerol (HPG) shell by the combination of a "grafting from" strategy with a ring-opening polymerization technique. The structure and morphology of the resulting UCNP-g-HPG nanohybrid were characterized in detail by Fourier transform infrared, (1)H NMR, thermogravimetric analysis, and transmission electron microscopy measurements. The results reveal that the amount of grafted HPG associated with the thickness of the HPG shell can be well tuned. UCNP-g-HPG shows high water dispersibility and strong and stable upconversion luminescence. On the basis of its numerous surface hydroxyl groups, UCNP-g-HPG can be tailored by a representative fluorescent dye rhodamine B to afford a UCNP-g-HPG-RB nanohybrid that simultaneously presents upconversion and downconversion luminescence. Preliminary biological studies demonstrate that UCNP-g-HPG shows low cytotoxicity, high luminescent contrast, and deep light penetration depth, posing promising potential for bioimaging applications.