Cancer is the second most frequent cause of death worldwide, with 28.4 million new cases expected for 2040. Despite de advances in the treatment, it remains a challenge because of the tumor heterogenicity and the increase in multidrug resistance mechanisms. Thus, gene therapy has been a potential therapeutic approach owing to its ability to introduce, silence, or change the content of the human genetic code for inhibiting tumor progression, angiogenesis, and metastasis. For the proper delivery of genes to tumor cells, it requires the use of gene vectors for protecting the therapeutic gene and transporting it into cells. Among these vectors, liposomes have been the nonviral vector most used because of their low immunogenicity and low toxicity. Furthermore, this nanosystem can have its surface modified with ligands (e.g., antibodies, peptides, aptamers, folic acid, carbohydrates, and others) that can be recognized with high specificity and affinity by receptor overexpressed in tumor cells, increasing the selective delivery of genes to tumors. In this context, the present review address and discuss the main targeting ligands used to functionalize liposomes for improving gene delivery with potential application in cancer treatment.

The convergence of 3D bioprinting and microfluidics has revolutionized the development of organ-on-a-chip platforms, offering unprecedented opportunities in biomedical research and tissue engineering. This comprehensive review delves into the latest advancements in these technologies, highlighting their significance and transformative potential. The introduction provides an overview of 3D bioprinting, microfluidics, and organ-on-a-chip systems, emphasizing their critical roles in replicating physiological conditions and enhancing the precision of biomedical studies. The review aims to move beyond fundamental concepts, focusing on recent innovations and applications that have propelled these technologies to the forefront of research. In the realm of 3D bioprinting, the review explores the evolution of bioprinting techniques, including extrusion-based, inkjet, and laser-assisted methods and polymer-based biomaterials as matrices for in vitro tissue modeling. Technological breakthroughs such as high-resolution bioprinting, multi-material printing, and advanced bioink development are discussed, showcasing their impact on creating complex tissue structures. Innovations in bioinks, including printable polymer-based hydrogels and decellularized matrix bioinks, are highlighted for their ability to replicate tissue microenvironments more accurately. The review also covers microfluidic innovations, detailing advances in design and fabrication, including 3D printing and sensor integration. Key innovations in fluid dynamics and tissue integration are examined, demonstrating how these advancements enhance tissue modeling and mimic physiological perfusion. Developing multi-organ-on-a-chip systems and connecting multiple tissue types for systemic studies are also explored. Hence, integrating 3D bioprinting and microfluidics is a focal point, with discussions on how their convergence enhances organ-on-a-chip platforms. The review concludes by examining current challenges, such as scalability and regulatory hurdles, and future directions, including emerging technologies like 4D bioprinting and AI-driven tissue design.

Animal testing for cosmetic ingredients and final products has been banned in Europe and is gaining legal force worldwide. However, the need for reliable testing methodologies remains for safety assessment of cosmetic ingredients. While new approach methodologies exist for many toxicological endpoints, some complex ones lack appropriate testing methods. Microphysiological systems (MPSs) have emerged as a promising tool to address this gap in pre-clinical testing, offering higher predictivity compared to animal models due to the phylogenetic distance between humans and animals. Moreover, they provide a more physiological approach than traditional in vitro testing by mimicking interconnections between different culture compartments as seen in complex organisms. This study presents a three-organ microfluidic MPS comprising skin, liver, and intestine equivalents. Combining this model with gene expression analysis, we evaluated toxicological endpoints of chemicals, demonstrating its potential for diverse applications. Our findings highlight the MPS model as a reliable and ethical method to be applied in an integrated approach for safety assessment in the cosmetic industry. It offers a promising strategy to evaluate toxicological endpoints for cosmetic ingredients and other chemicals, supporting the elimination of animal testing while ensuring consumer safety.

The rising incidence of skin cancer represents a significant public health challenge, not only due to its clinical burden but also its psychosocial implications, necessitating the development of innovative therapeutic strategies. Gene therapy-based interventions, particularly those employing multifunctional delivery systems, have shown promise in enhancing antitumor efficacy. Here, we present a nanostructured lipid carrier (NLC) engineered for the topical co-delivery of Bcl-2-targeting siRNA and 5-fluorouracil (5-FU). The NLCs exhibited a mean particle size of ∼200 nm, a PdI of 0.25, and a zeta potential of +49 mV. Drug loading achieved ∼7.6% with 85% encapsulation efficiency for 5-FU, and approximately 60% release over 8 h, following Higuchi kinetics. In vitro and ex vivo human skin permeation assays confirmed preferential retention of both agents in the epidermis with minimal transdermal diffusion. The co-loaded NLCs demonstrated enhanced cytotoxicity (IC₅₀: 8.17 µM/0.83 nM for 5-FU/siRNA in 2D cultures; 134.4 µM/8.67 nM in 3D spheroids), mediated by clathrin-dependent endocytosis and ∼60% uptake efficiency. Functional assays revealed significant inhibition of cell migration (∼60%) and proliferation (∼3-fold), alongside efficient Bcl-2 silencing and apoptosis induction. In vivo, the NLCs suppressed tumor growth in a xenograft model, reduced inflammatory markers (MPO, NAG, TNF-α), and promoted apoptosis without inducing extracellular matrix remodeling. These findings underscore the therapeutic potential of dual-acting lipid nanoparticles for localized treatment of squamous cell carcinoma via combinatorial gene silencing and chemotherapy, offering a promising platform for advanced topical oncologic therapies.

1. Single-cell proteomics (SCP) based on mass spectrometry has emerged as a powerful and transformative tool in clinical medicine research, bringing a holistic cellular view and a comprehensive ana...