Suping Li

Uncontrolled hemorrhage in trauma, surgical, organ-related, and endoscopic settings, particularly in patients receiving antiplatelet therapy, remains difficult to manage clinically. Here, we introduce a high phosphatidylserine (PS)–exposed procoagulant platelet (hPPL) derivative reprogrammed from isolated platelets via calcium ionophore A23187–induced apoptosis, enriched in surface PS and capable of driving rapid hemostasis. Retaining a protein profile akin to resting platelets, hPPLs robustly promoted platelet activation and aggregation in human- and rat-derived plasma and whole blood in vitro and demonstrated superior hemostatic efficacy compared with clinical thrombin and commercial hemostatic materials [microporous polysaccharide hemispheres (MPH) and FIBRILLAR] in murine liver injury and porcine gastric ulcer bleeding models, even under antiplatelet treatment. Mechanistically, hPPLs up-regulated prostaglandin E synthase (PTGES), thereby increasing prostaglandin E2 (PGE ₂ ) production and its receptor 3 (EP3)–mediated platelet activation, which reinforced PS-mediated clot formation. Our findings identified an apoptosis-driven PTGES-PGE ₂ -EP3 signaling axis that augmented PS-mediated coagulation in murine and porcine hemorrhage models and established the hPPL derivative as a topical hemostatic agent with translational potential for organ-related bleeding and distinct advantages in managing complex endoscopic hemorrhages under both physiological and coagulopathic conditions.

Natural biological systems achieve precise cellular control through multidimensional signaling architectures that integrate sequence specificity, structural dynamics, and conformational switching. While synthetic DNA networks have been engineered primarily using sequence programmability, exclusive reliance on this dimension constrains signaling range and integrated regulation. Here, we report an allosteric DNA computing framework enabling the simultaneous integration of sequence programmability with conformational dynamics for integrated multilevel signal processing. By encoding conformational signals within polythymidine loops (0 to 40 nucleotides), this system executes loop-dependent logic operations with expanded signaling ranges. Moreover, catalytic allosteric hairpin assemblies achieve ~30-fold signal amplification with enhanced signal-to-noise ratios. Concurrently, allosteric DNA neural networks discriminate conformational signals based on loop lengths (7 to 15 nucleotides) at two-nucleotide resolution. Crucially, microRNA-responsive versions of this framework regulate gene expression, thereby bridging conformational signaling with genetic control regulations in vivo. Collectively, this work establishes a conformational signal-processing paradigm for adaptive DNA computing, paving the way for advanced synthetic biology and precision therapeutics.

Supporting information for manuscript

Nanoparticles (NP) spanning diverse materials and properties have the potential to encapsulate and to protect a wide range of therapeutic cargos to increase bioavailability, to prevent undesired degradation, and to mitigate toxicity. Fulvestrant, a selective estrogen receptor degrader, is commonly used for treating patients with estrogen receptor (ER)–positive breast cancer, but its broad and continual application is limited by poor solubility, invasive muscle administration, and drug resistance. Here, we developed an active targeting motif-modified, intravenously injectable, hydrophilic NP that encapsulates fulvestrant to facilitate its delivery via the bloodstream to tumors, improving bioavailability and systemic tolerability. In addition, the NP was coloaded with abemaciclib, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6), to prevent the development of drug resistance associated with long-term fulvestrant treatment. Targeting peptide modifications on the NP surface assisted in the site-specific release of the drugs to ensure specific toxicity in the tumor tissues and to spare normal tissue. The NP formulation (PPFA-cRGD) exhibited efficient tumor cell killing in both in vitro organoid models and in vivo orthotopic ER-positive breast cancer models without apparent adverse effects, as verified in mouse and Bama miniature pig models. This NP-based therapeutic provides an opportunity for continual and extensive clinical application of fulvestrant, thus indicating its promise as a treatment option for patients with ER-positive breast cancer.Significance:A smart nanomedicine encapsulating fulvestrant to improve its half-life, bioavailability, and tumor-targeting and coloaded with CDK4/6 inhibitor abemaciclib to block resistance is a safe and effective therapy for ER-positive breast cancer.

Background . Advances in nanoparticle design technologies have enabled the development of numerous experimental molecular compositions that demonstrate high potential for improving traditional approaches to cancer treatment. However, only a few drugs successfully complete phase III clinical trials and receive approval for clinical use. Analysis of the advantages and disadvantages of nanomedicines, the challenges of their widespread medical application, and further development of this promising field are of undoubted interest to both experimental and clinical oncology. Material and Methods . The results of a search in the scientific databases PubMed, Medline, in the scientific electronic library eLibrary.ru, as well as in the clinical trials registration database https://clinicaltrials.gov were analyzed for the following queries – keywords: nanoparticles, nanomaterials, nanomedicines and cancer (nanoparticles, nanomaterials and nanomedicines for cancer). For this literature review, 60 relevant articles by internastional and domestic authors published between 2015 and 2025 were selected. Results. Nanosized molecular compositions offer advantages in cancer therapy primarily through selective tumor accumulation, which enables targeted delivery of antitumor agents and leads to increased therapeutic efficacy. The existing challenges in practical application of this group of drugs are associated with ensuring their stability and safety, as well as with the high variability of the tumor cell microenvironment. Conclusion . The prospects of nanodrug development focus on integrating various nanomaterials with targeted ligands to deliver antitumor and immunomodulatory agents directly to tumors, with a focus on personalized strategies that consider individual tumor characteristics.

In biological systems, molecular network functionalities are usually switched in a flexible, facile, and programmable manner. Mimicking this, substantial studies are directed towards developing synthetic DNA networks that exhibit similar function-switching capabilities, though often hindered by extensive molecular architecture changes and stringent condition controls, which result in a time-consuming and labor-intensive process. Here, we develop a base stacking-mediated allostery strategy to manipulate the DNA computing function switching with minimal molecular architecture changes, usually as few as 1-2 nucleotide changes. We implement up to 20 distinct logic function switching within DNAzyme networks. We also validate our function switching platform to implement totally 84 kinds of gene regulation patterns in cancer cell lines, demonstrating its utility in RNA sensing and green fluorescent protein regulation. This strategy offers a simplified alternative approach to enrich DNA regulations, with potential applications in DNA computing and bioengineering.

The immune‐suppressive microenvironment and extensive tumor angiogenesis are key contributors to the high recurrence and mortality rates of oral squamous cell carcinoma (OSCC). To address these challenges, a personalized 3D‐printed anti‐tumor vaccine (3D‐Vax‐L) is developed that integrates whole tumor antigens from postoperative tissue lysates with the angiogenesis inhibitor, lenvatinib. This vaccine not only possesses inherent adjuvant properties but also mimics the functions of lymph nodes through its porous structure, facilitating the recruitment and maturation of immune cells. In vivo studies in OSCC animal models, including mice and rabbits, demonstrate that 3D‐Vax‐L effectively recruits and matures immune cells at postoperative sites, inhibits angiogenesis and tumor recurrence, and extends survival time, all while maintaining a stable morphology and an excellent biosafety. Furthermore, 3D‐Vax‐L supports facial integrity post‐surgery, addressing physical challenges by preventing collapse and reducing the risk of aesthetic‐related disorders. These findings suggest that 3D‐Vax‐L is a promising therapeutic technique for preventing post‐surgical OSCC relapse, particularly as it offers a new strategy for immune system activation and demonstrates significant potential for clinical translation.

Cancer represents a major worldwide disease burden marked by escalating incidence and mortality. While therapeutic advances persist, developing safer and precisely targeted modalities remains imperative. Nanomedicines emerges as a transformative paradigm leveraging distinctive physicochemical properties to achieve tumor-specific drug delivery, controlled release, and tumor microenvironment modulation. By synergizing passive enhanced permeation and retention effect-driven accumulation and active ligand-mediated targeting, nanoplatforms enhance pharmacokinetics, promote tumor microenvironment enrichment, and improve cellular internalization while mitigating systemic toxicity. Despite revolutionizing cancer therapy through enhanced treatment efficacy and reduced adverse effects, translational challenges persist in manufacturing scalability, longterm biosafety, and cost-efficiency. This review systematically analyzes cutting-edge nanoplatforms, including polymeric, lipidic, biomimetic, albumin-based, peptide engineered, DNA origami, and inorganic nanocarriers, while evaluating their strategic advantages and technical limitations across three therapeutic domains: immunotherapy, chemotherapy, and radiotherapy. By assessing structure-function correlations and clinical translation barriers, this work establishes mechanistic and translational references to advance oncological nanomedicine development.