Resolving the conflict between cytoplasmic delivery efficiency and biocompatibility of small interfering RNA (siRNA) carriers is crucial for the clinical translation of siRNA therapies. In this study, we developed a highly biocompatible and fully biodegradable siRNA delivery system, MnCO₃@BSA/Zn²⁺/siRNA (MRna), using bovine serum albumin (BSA) and essential metal ions. This carrier leverages the high affinity of Zn²⁺ and Mn²⁺ for biomolecules (BSA and siRNA) to achieve siRNA loading and protection through a water-phase “one-pot” self-assembly and biomineralization process, achieving a 90% siRNA encapsulation rate. Additionally, the nanoscale mineral particles allow rapid disintegration in the endosomal environment to release 55% of siRNA and facilitate its endosomal escape by mediating the “proton sponge effect”. Therefore, the colocalization coefficient of siRNA with the lysosome is only 0.18. Ultimately, MRna loaded with CD47 siRNA effectively reduces CD47 expression at both mRNA and protein levels in tumor cells to lower than 50% of the original, showing efficiency comparable to the commercial transfection reagent Lipo2000. Overall, this study provides a more convenient, efficient and biocompatible strategy for designing siRNA delivery systems.

An HPLC analytical method was developed to determine the related substances in carbetocin injection. The method was performed on a Waters Xbridge C₁₈ column (150 mm×3 mm, 3.5 μm) with 0.30 mg/mL ammonium acetate-19% acetonitrile aqueous solution as mobile phase A and mobile phase A-acetonitrile (1∶1) as mobile phase B. The detection wavelength was 220 nm. Gradient elution was performed at the flow rate of 0.8 mL/min and the column temperature of 60℃. The method was validated for system applicability, specificity, linearity and range, accuracy, with the results that the 9 impurities of carbetocin injection showed good linearity (R²>0.999) with peak area in their respective concentration range, and that the method had good precision (RSD<5%). This method is suitable for the simultaneous determination of carbetocin and its 9 impurities in carbetocin injection and can provide a theoretical basis for the quality control of the carbetocin injection.

Despite the promise of nanomedicines leveraging the enhanced permeability and retention (EPR) effect for tumor targeting, their clinical translation remains hindered due to physiological barriers, rapid clearance, and poor intratumoral diffusion. In situ self-assembly of nanomedicines within tumors offers a promising strategy to enhance tumor accumulation. However, significant challenges persist. Herein, our findings reveal that tumor-infiltrating erythrocytes demonstrate the capacity to endogenously synthesize self-assembled nanomedicine with clinically approved small-molecule drug. Attenuated Salmonella Typhimurium VNP20009 (VNP) can induce tumor-specific erythrocyte infiltration. Erythrocytes infiltrating the tumor site are phagocytosed by tumor cells and degraded into ferrous ions through the action of heme oxygenase. In the presence of zoledronic acid, ferrous irons interact with the zoledronic acid, resulting in the intracellular self-assembly of nanoparticles within tumor cells. These nanoparticles exhibit peroxidase-mimetic activity, and continuously catalyze the generation of reactive oxygen species (ROS) within the tumor, ultimately inducing tumor cell apoptosis. Therefore, this bioengineered therapeutic strategy that harnesses erythrocyte phagocytosis to drive tumor-specific intracellular self-assembly of peroxidase-mimetic nanoparticles may open up new nanotechnology for drug delivery and improve antitumor therapy.