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The rapid development of CRISPR/Cas9 systems has opened up tantalizing prospects to sensitize cancers to chemotherapy using efficient targeted genome editing, but safety concerns and possible off-target effects of viral vectors remain a major obstacle for clinical application. Thus, the construction of novel nonviral tumor-targeting nanodelivery systems has great potential for the safe application of CRISPR/Cas9 systems for gene–chemo-combination therapy. Here, we report a polyamidoamine-aptamer-coated hollow mesoporous silica nanoparticle for the co-delivery of sorafenib and CRISPR/Cas9. The core–shell nanoparticles had good stability, enabled ultrahigh drug loading, targeted delivery, and controlled-release of the gene–drug combination. The nanocomplex showed >60% EGFR-editing efficiency without off-target effects in all nine similar sites, regulating the EGFR-PI3K-Akt pathway to inhibit angiogenesis, and exhibited a synergistic effect on cell proliferation. Importantly, the co-delivery nanosystem achieved efficient EGFR gene therapy and caused 85% tumor inhibition in a mouse model. Furthermore, the nanocomplex showed high accumulation at the tumor site in vivo and exhibited good safety with no damage to major organs. Due to these properties, the nanocomplex provides a versatile delivery approach for efficient co-loading of gene–drug combinations, allowing for precise gene editing and synergistic inhibition of tumor growth without apparent side effects on normal tissues.

Solution‐processed nickel oxide nanocrystals (NiOx NCs) ink can be facilely applied to deposit NiOx thin films as the hole transport layer (HTL) for perovskite solar cells (PSCs). Both the efficiency and stability of the corresponding PSCs depend significantly on the size and the energy levels of the as‐synthesized NiOx NCs; however, previous studies have shown that these two aspects can be hardly controlled synchronously to maximize the device performance. Herein, a novel synthesis of highly dispersed NiOx NCs is demonstrated by employing tetraalkylammonium hydroxides (TAAOHs, alkyl = methyl, ethyl, propyl, butyl) as precipitating bases, where the varied alkyl chain lengths of TAAOHs enable the size control of the NiOx NCs and the subsequent altering of their Ni3+ contents, leading to tunable energy levels of the NiOx thin films. With the longest butyl chain, the smallest crystal size and the optimal energy level alignment at the NiOx/perovskite interface are achieved. After further passivating the detrimental Ni3+ species on the surface of NiOx HTL, a remarkable power conversion efficiency (PCE) approaching 23% is obtained, which is one of the highest PCEs reported for NiOx‐based inverted PSCs. Furthermore, the unencapsulated device exhibits excellent ultraviolet stability, which maintains ≈87% of its PCE after 200 h exposure.

Oral protein delivery is considered a cutting-edge technology to improve patients’ quality of life, offering superior patient compliance and convenience compared with injections. However, oral protein formulation has stagnated because of the instability and inefficient penetration of protein in the gastrointestinal tract. Here, we used acid-resistant metal-organic framework nanoparticles (UiO-68-NH 2 ) to encapsulate sufficient insulin and decorated the exterior with targeting proteins (transferrin) to realize highly efficient oral insulin delivery. The UiO-68-NH 2 nanocarrier with proper pore size achieved high insulin loading while protecting insulin from acid and enzymatic degradation. Through receptor-mediated transcellular pathway, the transferrin-coated nanoparticles realized efficient transport across the intestinal epithelium and controlled insulin release under physiological conditions, leading to a notable hypoglycemic effect and a high oral bioavailability of 29.6%. Our work demonstrates that functional metal-organic framework nanoparticles can protect proteins from the gastric environment and overcome the intestinal barrier, thus providing the possibility for oral biomacromolecule delivery.