Chi Yao

High‐efficiency and specific isolation of exosomes from diverse biological fluids remains a major challenge for clinical diagnostics. Herein, we developed an aptamer‐functionalized dual‐network hydrogel platform for the specific enrichment and non‐destructive release of exosomes. This study proposes an aptamer‐functionalized dual‐network hydrogel technology aimed at achieving the specific separation and non‐destructive release of exosomes from complex biological samples. Using a sacrificial nickel foam template, polyacrylamide and polyacrylic acid were sequentially polymerized to construct a stable, interconnected macroporous hydrogel framework, which minimized flow resistance for rapid sample permeation. To build the affinity interface, circular DNA templates were chemically crosslinked into the accessible carboxyl groups of the polyacrylic acid segments, followed by in situ rolling circle amplification (RCA) to generate long DNA concatamers rich in repetitive CD63 aptamer sequences for efficient target capture. Meanwhile, polyacrylic acid is expected to reduce the non‐specific adsorption of the composite hydrogel toward contaminating proteins, thereby improving the purity of the isolated exosomes. Finally, introducing complementary DNA displacement strands enables efficient, mild vesicle release via competitive hybridization, fully preserving structural integrity and cellular uptake ability. This bio‐functionalized hydrogel system provides a gentle, efficient, and reliable methodology for high‐purity exosome isolation, offering a promising tool for advanced biomedical applications.

Nucleic acid‐based gene therapeutics hold great potential for precisely treating pancreatic ductal adenocarcinoma (PDAC), yet their clinical translation remains challenged by the lack of efficient delivery platforms capable of simultaneously minimizing payload leakage, intrinsic toxicity, and immunogenicity. Herein, we report an acid‐activatable nucleic acid nano‐prodrug based on rolling circle replication, which directly integrates a large number of amplified Cas12/crRNA ribonucleoproteins (RNPs) and antisense oligonucleotides (ASOs) with minimal excipients, achieving tumor‐specific activation for PDAC combined gene therapy. The nano‐prodrug is assembled from a polymeric crRNA chain conjugated with Cas12a (Pro‐RNPs) and a polymeric ASOs chain (Pro‐ASOs)—the latter incorporating AS1411 aptamers for cancer targeting and HhaI cleavage sites for stimuli‐responsive release—while being surface‐loaded with acid‐degradable polymer‐coated HhaI enzymes. Upon PDAC uptake, the nano‐prodrug is activated within acidic lysosomes through degradation of HhaI enzymes’ polymer coating. HhaI cleaves specific recognition sites while overexpressed ribonuclease H hydrolyzes the RNA strand in DNA‐RNA heteroduplexes. These combined cleavage events disrupt the nano‐prodrug, enabling efficient co‐release of ASOs and Cas12a/crRNA RNPs for precise gene silencing and editing. In vivo studies in PDAC‐bearing mice demonstrate potent antitumor activity with minimal systemic toxicity or immunogenicity, presenting a promising strategy for precision gene therapy in pancreatic cancer.

Artificial cells are synthetic systems that emulate lifelike behaviors through multilevel molecular architectures capable of sensing and processing information. The high programmability and structural designability of DNA make it one of the most powerful molecular tools for bottom‐up artificial cell construction. This review systematically summarizes the expanding roles of DNA in artificial cells, ranging from transmembrane receptors and nanopores to internal reaction networks and cytoskeletal structures and liquid condensates, highlighting the structural and functional units of DNA, as well as its applications in hierarchical organization and communication with living cells. At the same time, we discuss the potential breakthroughs in DNA hybrid materials and nonequilibrium information processing for future artificial cell engineering.

This review highlights DNA-based hybrid nanoparticles for cancer therapy, covering gene editing, energy-activated treatments, immunotherapy and theranostics.

This review summarizes the construction strategies and key properties of DNA condensates, highlighting their emerging applications in artificial cells, biosensing and diagnostics, cellular regulation, and drug delivery.

Deoxyribonucleic acid (DNA) has emerged as a highly programmable, biocompatible and structurally versatile building block for the construction of multifunctional biomaterials, presenting broad application potential in biomedicine.

Photodynamic therapy (PDT) holds significant promise for treating pancreatic cancer by utilizing photosensitizers to generate reactive oxygen species (ROS) that induce tumor cell death. However, the therapeutic efficacy of PDT is hindered by inadequate ROS accumulation. Herein, we develop a DNA nanoflower that enables the controlled codelivery of Cas9 ribonucleoprotein (RNP), hemin, and chlorin e6 for synergistic PDT. The Cas9 RNP selectively knocks out the antioxidant regulator nuclear factor E2-related factor 2 (Nrf2), thereby increasing cancer cells' sensitivity to ROS. Simultaneously, the G-quadruplex/hemin complex catalyzes the conversion of endogenous H₂O₂ into O₂, alleviating tumor hypoxia and supplying additional oxygen for PDT. This synergistic approach substantially amplifies ROS accumulation by attenuating ROS elimination and enhancing ROS generation, demonstrating high gene editing efficiency, significant Nrf2 down-regulation, elevated apoptosis, and remarkable antitumor efficacy in pancreatic cancer cells and a mouse model, underscoring the potential for precision medicine.

This review gives an overview of RCA/RCT-based nanocarriers for nucleic acid drug delivery, systematically summarizing their nanoization strategies, drug loading approaches, targeting modalities, and controlled release mechanisms.