Correction: Clodronate-nintedanib-loaded exosome-liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity.

Correction for 'Clodronate-nintedanib-loaded exosome-liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity' by Keqin Ji et al., Biomater. Sci., 2022, 10, 702-713, https://doi.org/10.1039/D1BM01663F.

Biological Hyperthermia-Inducing Nanoparticles for Specific Remodeling of the Extracellular Matrix Microenvironment Enhance Pro-Apoptotic Therapy in Fibrosis.

The extracellular matrix (ECM) is a major driver of fibrotic diseases and forms a dense fibrous barrier that impedes nanodrug delivery. Because hyperthermia causes destruction of ECM components, we developed a nanoparticle preparation to induce fibrosis-specific biological hyperthermia (designated as GPQ-EL-DNP) to improve pro-apoptotic therapy against fibrotic diseases based on remodeling of the ECM microenvironment. GPQ-EL-DNP is a matrix metalloproteinase (MMP)-9-responsive peptide, (GPQ)-modified hybrid nanoparticle containing fibroblast-derived exosomes and liposomes (GPQ-EL) and is loaded with a mitochondrial uncoupling agent, 2,4-dinitrophenol (DNP). GPQ-EL-DNP can specifically accumulate and release DNP in the fibrotic focus, inducing collagen denaturation through biological hyperthermia. The preparation was able to remodel the ECM microenvironment, decrease stiffness, and suppress fibroblast activation, which further enhanced GPQ-EL-DNP delivery to fibroblasts and sensitized fibroblasts to simvastatin-induced apoptosis. Therefore, simvastatin-loaded GPQ-EL-DNP achieved an improved therapeutic effect on multiple types of murine fibrosis. Importantly, GPQ-EL-DNP did not induce systemic toxicity to the host. Therefore, the nanoparticle GPQ-EL-DNP for fibrosis-specific hyperthermia can be used as a potential strategy to enhance pro-apoptotic therapy in fibrotic diseases.

Clodronate-nintedanib-loaded exosome-liposome hybridization enhances the liver fibrosis therapy by inhibiting Kupffer cell activity.

Liver fibrosis therapy remains limited due to the inefficiency of drug delivery and inflammation induced by Kupffer cells. In this study, an exosome-liposome hybrid drug delivery system (LIEV) was developed to increase the efficacy of clodronate (CLD)-inhibition of Kupffer cells and to effectively deliver nintedanib (NIN) to liver fibroblasts to ensure enhanced anti-fibrosis therapy. CLD and NIN co-loaded LIEV (CLD/NIN@LIEV) exerted non-specific inhibition of phagocytosis by Kupffer cells, reduced inflammatory cytokines, and showed homologous homing properties mediated by fibroblast-derived exosomes, thereby achieving superior antifibrotic effects in a CCl4-induced fibrosis mouse model by inhibiting the proliferation of fibroblasts. Furthermore, the inhibited Kupffer cells regenerated within 10 days after dosage withdrawal. Unlike carrier-free NIN treatment, CLD/NIN@LIEV induced a marked decrease in liver enzymes, indicating improved safety and anti-fibrosis efficacy. These results indicate its great potential for treatment with the combined anti-fibrosis agent and Kupffer cell inhibition strategies to enhance the liver fibrosis therapy.