Biology subjects

Saarela, S.

Publications and source records attributed to Saarela, S..

3 recordsLinked to original sources

bioRxiv2026

Bioinspired Virus-Like Porous Silica Amplify Lipid-Mediated mRNA Delivery

Lipid nanoparticles (LNPs) have demonstrated strong potential in COVID-19 mRNA vaccines nevertheless they still face the challenges in low mRNA delivery efficacy. Virus-like porous silica (VLPSi) nanoparticles (NPs) represent a promising biomimetic delivery platform because their spiked morphology may enhance cellular internalization and promote endosomal membrane disruption. However, the application of VLPSi for mRNA has been rarely explored. In this study, hybrid lipid-VLPSi NPs were developed by combining VLPSi with either lipoplexes (LPs) or LNPs. The effects of lipid types, mass ratio of different compositions, and amine modifications of VLPSi on mRNA delivery were studied. The results demonstrated that both LP and LNP could be successfully integrated with VLPSi to form hybrid delivery systems for mRNA transfection. VLPSi could significantly enhance mRNA delivery of both LPs and LNPs due to improved cellular uptake, structural stabilization of the mRNA complex, and enhanced endosomal escape mediated by the rigid virus-like surface architecture. Among the tested lipid formulations, the ionizable lipid ALC-0315 and helper lipid DOPE with mass ratio of 5:3 was the most effective lipid composition to be integrated with VLPSi, showing the highest mRNA delivery performance. In addition, amino modification of VLPSi was found to be a critical factor for efficient mRNA delivery. Hybrid LNPs containing amino-modified VLPSi showed significantly higher transfection efficiency than those containing unmodified VLPSi. Notably, amino-modified LNP-VLPSi achieved up to fivefold higher gene expression than conventional LNPs. Overall, this study establishes VLPSi as an efficient platform for amplifying lipid-mediated mRNA delivery. Owing to its straightforward integration into widely used LNP systems, VLPSi offers an adaptable and effective strategy for advancing next-generation mRNA therapeutics.

bioengineering↗

bioRxiv2026

Biomimetic virus-like mesoporous silica nanoparticles activate NK cells indirectly via monocyte crosstalk

Cancer immunotherapies show clinical promise but often rely on T-cell priming and are limited by tumor heterogeneity and the immunosuppressive tumor microenvironment (TME). Innate immune activation offers a complementary strategy, with specific aim in natural killer (NK) cell activation for antigen-independent response. Biomimetic nanoparticles combining virus-like morphology with cell membrane (CM) coating offer a strategy to engage this innate immune axis. This study investigates virus-like mesoporous silica nanoparticles (VLPSi) with tunable spikes, surface functionalization, and CM coating as innate immunity modulators. Optimization revealed that longer spikes, amine functionalization, and CM coating synergistically enhance NK cell activation within human PBMCs, as indicated by CD69/CD25 upregulation and IFN-{gamma} secretion. CD14+ monocyte depletion attenuated activation, identifying monocyte-dependent crosstalk as a key mechanism. In purified NK cells, engineered CM-coated VLPSi induced early activation and supported feeder-free expansion. These results define topology, surface chemistry, and CM coating as parameters for innate immune modulation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=69 SRC="FIGDIR/small/720074v1_ufig1.gif" ALT="Figure 1"> View larger version (18K): org.highwire.dtl.DTLVardef@db5cdorg.highwire.dtl.DTLVardef@1ab41eorg.highwire.dtl.DTLVardef@127428dorg.highwire.dtl.DTLVardef@82609a_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2024

Biomimetic porous silicon for rationally engineered combination therapy to induce immunogenic cell death

Combined chemo-photothermal therapy (CHT-PTT) is a promising treatment for metastatic cancers. It enables the synergistic induction of immunogenic cell death (ICD), while sensitising suppressive tumour microenvironment to immunotherapy. To induce ICD, the rational design of a combined CHT-PTT regimen remains unclear. In the present study, black porous silicon nanoparticles (BPSi NPs) were utilized as both drug carriers and photothermal conversion agents. To enhance their colloidal stability and homotypic targeting, BPSi NP surfaces were modified with polyethylene glycol and further coated with cancer cell membranes (CMs). Six chemotherapeutic drugs with different cell growth inhibition mechanisms were tested against metastatic MDA-MB-231 breast cancer cells to evaluate their ICD induction potentials. Finally, in the combined CHT-PTT, the effect of temperature was evaluated. Based on the analysis of ICD markers, high-mobility group box 1 and calreticulin proteins, we found that bromodomain-containing protein 4 inhibitor, (+)-JQ-1 (JQ1) was the optimal drug, and the mild-hyperthermia temperature of 45 {degrees}C was the best temperature setting in the combined CHT-PTT to induce ICD. Thus, our study provides rationally designed CHT-PTT regimen for efficient cancer treatment with high efficacy and low side effects.

bioengineering↗