Biology subjects

Happonen, E.

Publications and source records attributed to Happonen, E..

2 recordsLinked to original sources

bioRxiv2026

Engineering morphology of tetrasulfide-incorporated mesoporous silica nanoparticles for enhanced mRNA delivery

Lipid nanoparticles (LNPs) are the most studied nanocarrier for mRNA delivery, yet their broader application remains limited due to suboptimal cellular uptake, low efficacy in mRNA delivery, and poor stability. In this study, we report a novel tetrasulfide-incorporated virus-like porous silica (VLPSi) nanoparticle as a safe and efficient platform to enhance LNP-mediated mRNA delivery. By systematically tuning the synthesis parameters, a series of nanoparticles with distinct morphologies and architectures were obtained, enabling the study of how tetrasulfide and particle morphology affect mRNA delivery. The performance of VLPSi was optimized by evaluating cellular uptake, cytotoxicity, and transfection performance with different lipid and mRNA payloads across multiple cell types. The results showed that increasing the length and number of spikes on the VLPSi surface significantly improved cellular uptake efficiency and subsequent mRNA expression. Mechanistically, the enhanced delivery arose from the combined effect from the nanospikes and intracellular tetrasulfide degradation. Furthermore, the nanoparticles significantly enhanced the stability of mRNA. Overall, these findings establish a structure-function relationship between virus-like topography, biodegradable silica chemistry, and mRNA delivery. This work provides a structurally tunable, biodegradable, and highly effective bioinspired nanoplatform to enhance mRNA delivery.

biochemistry↗

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↗