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CRISPR/Cas9 genome editing has gained rapidly increasing attentions in recent years, however, the translation of this biotechnology into therapy has been hindered by efficient delivery of CRISPR/Cas9 materials into target cells. Direct delivery of CRISPR/Cas9 system as a ribonucleoprotein (RNP) complex consisting of Cas9 protein and single guide RNA (sgRNA) has emerged as a powerful and widespread method for genome editing due to its advantages of transient genome editing and reduced off-target effects. In this review, we summarized the current Cas9 RNP delivery systems including physical approaches and synthetic carriers. The mechanisms and beneficial roles of these strategies in intracellular Cas9 RNP delivery were reviewed. Examples in the development of stimuli-responsive and targeted carriers for RNP delivery are highlighted. Finally, the challenges of current Cas9 RNP delivery systems and perspectives in rational design of next generation materials for this promising field will be discussed.

While China's \"Double Reduction Policy\" has expanded children's out-of-school time, research has predominantly focused on STEM and sports extracurricular activities, often overlooking the specific cognitive and academic role of the visual arts. Addressing this gap, this systematic review synthesizes 11 eligible studies to explore the association between out-of-school visual art activities and academic performance in Chinese children, while identifying key moderating factors. Conducted according to the PRISMA 2021 guidelines, the review finds that visual art engagement strengthens spatial reasoning, working memory, and creative problem-solving, thereby improving standardized test scores and school readiness. However, the benefits are not linear; they are shaped by a threshold model, in which excessive participation diminishes returns, and are moderated by socioeconomic access, parental involvement, and gender. Theoretically, this review underscores the novelty of this nonlinear relationship within the Chinese context. These findings highlight the need for policies that ensure equitable access to arts education and guide parents in fostering balanced, high-quality artistic engagement to support holistic cognitive development. Future research should investigate long-term effects and expand methodological and geographical scopes.

Direct delivery of proteins into cells avoids many drawbacks of gene delivery, and thus has emerging applications in biotherapy. However, it remains a challenging task owing to limited charges and relatively large size of proteins. Here, we report an efficient protein delivery system via the co-assembly of fluoroamphiphiles and proteins into nanoparticles. Fluorous substituents on the amphiphiles play essential roles in the formation of uniform nanoparticles, avoiding protein denaturation, efficient endocytosis, and maintaining low cytotoxicity. Structure-activity relationship studies reveal that longer fluorous chain length and higher fluorination degree contribute to more efficient protein delivery, but excess fluorophilicity on the polymer leads to the pre-assembly of fluoroamphiphiles into stable vesicles, and thus failed protein encapsulation and cytosolic delivery. This study highlights the advantage of fluoroamphiphiles over other existing strategies for intracellular protein delivery. Proteins can serve as means of medical treatment, but their efficient delivery to cells is difficult. Here, the authors present a type of polymers, fluoroamphiphiles, acting as chemical chaperones that can facilitate the import of proteins into the inner compartment, i.e. cytosol, of cells.

Cancer metastases and recurrence after surgical resection remain an important cause of treatment failure. Here we demonstrate a general strategy to fabricate personalized nanovaccines based on a cationic fluoropolymer for post-surgical cancer immunotherapy. Nanoparticles formed by mixing the fluoropolymer with a model antigen ovalbumin, induce dendritic cell maturation via the Toll-like receptor 4 (TLR4)-mediated signalling pathway, and promote antigen transportation into the cytosol of dendritic cells, which leads to an effective antigen cross-presentation. Such a nanovaccine inhibits established ovalbumin-expressing B16-OVA melanoma. More importantly, a mix of the fluoropolymer with cell membranes from resected autologous primary tumours synergizes with checkpoint blockade therapy to inhibit post-surgical tumour recurrence and metastases in two subcutaneous tumour models and an orthotopic breast cancer tumour. Furthermore, in the orthotopic tumour model, we observed a strong immune memory against tumour rechallenge. Our work offers a simple and general strategy for the preparation of personalized cancer vaccines to prevent post-operative cancer recurrence and metastasis.A fluoropolymer-based cancer nanovaccine that delivers antigens directly to the cytosol of dendritic cells and elicits strong antitumour immune responses inhibiting tumour growth in animal models can be used to produce personalized treatment for post-surgical immunotherapy.

Single-strand oligonucleotides provide promising potential as new therapeutics towards various diseases. However, the efficient delivery of oligonucleotide therapeutics is still challenging due to their susceptibility to nuclease degradation and the lack of effective carriers for condensation. In this study, we reported the use of natural polyphenol to facilitate the condensation of single-strand oligonucleotides by cationic polymers. Green tea catechin complexed with single-strand oligonucleotides to form anionic nanoparticles, which were further coated by low molecular weight cationic polymers to increase their cell internalization. The resulting core-shell structured nanoparticles, so-called green nanoparticles (GNPs), showed improved cargo stability, and achieved high efficiency in the delivery of several types of single-strand oligonucleotides including antisense oligonucleotides, anti-miRNA, and DNAzyme. This study provides a facile strategy for the efficient delivery of single-strand oligonucleotides.

RNA interference with the ability to specifically silence target genes has shown great potential to treat various diseases. The primary challenge for RNA interference is to effectively and selectively deliver genetic materials such as small interfering RNA (siRNA) to targeted tissues and cells in vivo. Numerous efforts have been made to overcome the extracellular and intracellular barriers during siRNA delivery. In this review, we focused on most recent advances in the design of functional polymers to achieve efficient siRNA delivery via addressing the various parameters, including siRNA binding, serum stability, specific targeting, tissue penetration, cellular internalization, endosomal escape, and intracellular siRNA release. The beneficial roles of assembled polymer nanostructures and polymer‐based hybrid nanocomposites in siRNA delivery were also reviewed. Finally, the challenges and perspectives in the future development of polymer‐based siRNA delivery systems will be discussed. RNAi‐mediated gene therapy possesses high specificity, efficiency, and simplicity, which makes siRNA quickly the most popular gene regulation tool. Cationic polymers could be conveniently designed to address the multiple barriers during siRNA delivery including siRNA binding, serum stability, cell selectivity, cellular uptake, endosome escape, and intracellular siRNA release, and hence have shown great potential in siRNA delivery.

Mitophagy is crucial for the selective autophagic degradation of damaged mitochondria, helping to maintain both mitochondrial and cellular homeostasis. Here, we report a fluoroalkylated polypyridinium that specifically targets mitochondria and exhibits high activity in mitophagy induction. The polymer effectively restores mitochondrial function and alleviates the inflammatory response in foam cells by activating mitophagy, and displays inherent red fluorescence under physiological conditions, allowing for direct tracing of its biodistribution in cells and in vivo. Besides, the polymer nanoparticle shows high serum stability due to the antifouling properties of fluoroalkyl tags. After intravenous administration, the nanoparticle reduces oxidative stress, promotes mitophagy, and decreases cellular senescence in atherosclerotic plaques, contributing to high therapeutic efficacy. This study presents an innovative and effective strategy for the treatment of atherosclerosis and other mitochondrial dysfunction-related inflammatory conditions. Liang, Ruan, Wang, and colleagues present a serum-stable, red-fluorescent nanoparticle that targets mitochondria, induces mitophagy, and effectively reduces atherosclerotic plaques in mice, constituting a promising nanomedicine for cardiovascular diseases.

Lipid nanoparticles (LNPs) have been successful in delivering nucleic acids like siRNA and mRNA, but face challenges in protein delivery due to limited protein encapsulation and endosome escape. In this study, a family of LNPs is developed with robust high efficiency in addressing the multiple barriers in cytosolic protein delivery by incorporating clinically approved ionizable lipids into traditional cationic LNPs. The combination of cationic and ionizable lipids enables efficient protein binding and endosomal escape. Optimized LNPs efficiently deliver various proteins, including antibodies, enzymes, toxins, and Cas9 into living cells with reserved functions. Moreover, the designed LNPs show high serum stability during protein delivery, and the serum albumin adsorbed on LNPs facilitates protein delivery via albumin receptor‐mediated endocytosis, enabling highly efficient protein delivery in vivo. The optimized LNPs successfully deliver therapeutic proteins such as saporin and interleukin‐10 (IL‐10) to inhibit tumor growth in several animal models. The IL‐10 loaded LNPs enhanced the proliferation and cytotoxicity of T cells and improved the antitumor effect of adoptive transferred OT‐1 CD8+ T cells to melanoma. This study expands the applications of LNPs for the delivery of biomacromolecules, and the developed LNP formulations have enormous potential for the delivery of protein therapeutics to treat various diseases. This study develops lipid nanoparticles (LNPs) combining cationic and ionizable lipids for efficient cytosolic protein delivery. Optimized LNPs deliver functional proteins, including antibodies, enzymes, and Cas9, with high serum stability and albumin‐mediated endocytosis. They enable therapeutic delivery of saporin and IL‐10, inhibiting tumor growth and enhancing T cell activity, showcasing potential for protein therapeutic applications in disease treatment.

Osteosarcoma is a malignant bone cancer usually characterized by symptoms of bone loss due to pathologically enhanced osteoclast activity. Activated osteoclasts enhance bone resorption and promote osteosarcoma cell progression by secreting various cytokines. Intercepting the detrimental interplay between osteoclasts and osteosarcoma cells is considered as an option for osteosarcoma treatment. Here, a bone‐targeted fluoropeptide nanoparticle that can inhibit the nuclear factor kappa B (NF‐κB) signaling in both osteoclasts and osteosarcoma to address the above issue is developed. The NF‐κB essential modulator binding domain (NBD) peptide is conjugated with a fluorous tag to improve its proteolytic stability and intracellular penetration. The NBD peptide is efficiently delivered into cells after fluorination to induce apoptosis of osteocarcoma cells, and inhibits osteoclasts differentiation. The fluorous‐tagged NBD peptide is further co‐assembled with an oligo (aspartic acid) terminated fluoropeptide to form bone‐targeted peptide nanoparticles for osteosarcoma treatment. The targeted nanoparticles efficiently inhibited tumor progression and osteosarcoma‐induced bone destruction in vivo. This co‐assembled fluoropeptide nanoplatform proposed in this study offers a promising approach for targeted and intracellular delivery of peptide therapeutics in the treatment of various diseases. A novel bone‐targeted fluorous NBD nanoparticle (DN‐F) effectively inhibits osteoclast differentiation and osteosarcoma growth by disrupting the NF‐κB signaling pathway, demonstrating enhanced bone‐targeting and suppression of bone destruction, while providing a versatile platform for future peptide‐based nanomedicines.

The opportunities and challenges of using dendrimers to improve drug delivery Among pharmaceutical and biomedical researchers, the use of dendrimers in drug delivery systems has attracted increasing interest.In particular, researchers have noted that the volume of a dendrimer increases when it has a positive charge.