Comparative evaluation of four nanocarriers in shrimp larvae and transcriptomic dissection of mesoporous silica nanoparticle-induced stress

• Four nanocarriers show distinct toxicity profiles in shrimp larvae. • MSN causes highest mortality and telson defects at early stages. • TNP and LNP show best biocompatibility and suit gene delivery use. • MSN triggers stage specific DEGs in metabolism, proteolysis and immunity. To evaluate the biocompatibility of various nanomaterials in aquatic invertebrates and their biocompatibility profiles relevant to gene delivery applications, this study systematically compares the effects of four representative nanocarriers—mesoporous silica nanoparticles (MSN), chitosan derivatives (CTMT), PEI–PEG copolymers (TNP), and lipid nanoparticles (LNP)—across four developmental stages of Penaeus monodon (Nauplius, Zoea, Mysis, and Post-larva). Acute effects on larval survival and development, tissue injury, and molecular responses were comprehensively assessed through mortality rates, morphological abnormalities, and multichannel fluorescence staining. Among the tested materials, MSN induced the most pronounced cellular damage and lethality at all stages, whereas TNP and LNP caused lower mortality, fewer larval malformations, and weaker cellular stress responses, indicating superior biocompatibility. Transcriptomic analysis revealed that MSN exposure triggered extensive differential gene expression associated with energy metabolism, protease regulation, and immune response, displaying distinct stage-specific patterns. Core gene network analysis identified RHOA, CASP1 , and Spn88Ea as key mediators potentially involved in MSN-induced apoptosis and stress responses. Collectively, the findings indicate that TNP and LNP exhibit higher biocompatibility and may represent safer candidates for future nucleic-acid delivery studies, whereas MSN, despite its structural advantages, requires stringent control of dosage and exposure duration prior to application. This study provides essential data and theoretical support for the selection and safety evaluation of nano-delivery systems in aquatic animals.