The extracellular matrix (ECM)-and its mechanobiology-regulates key cellular functions that drive tumor growth and development. Accordingly, mechanotherapy is emerging as an effective approach to treat fibrotic diseases such as cancer. Through restoring the ECM to healthy-like conditions, this treatment aims to improve tissue perfusion, facilitating the delivery of chemotherapies. In particular, the manipulation of ECM is gaining interest as a valuable strategy for developing innovative treatments based on nanoparticles (NPs). However, further progress is required; for instance, it is known that the presence of a dense ECM, which hampers the penetration of NPs, primarily impacts the efficacy of nanomedicines. Furthermore, most 2D in vitro studies fail to recapitulate the physiological deposition of matrix components. To address these issues, a comprehensive understanding of the interactions between the ECM and NPs is needed. This review focuses on the main features of the ECM and its complex interplay with NPs. Recent advances in mechanotherapy are discussed and insights are offered into how its combination with nanomedicine can help improve nanomaterials design and advance their clinical translation.
- Klíčová slova
- ECM, cancer therapy, mechanobiology, mechanotherapy, nanomedicine,
- MeSH
- extracelulární matrix * metabolismus MeSH
- lidé MeSH
- nádory * metabolismus farmakoterapie terapie MeSH
- nanočástice * chemie MeSH
- nanomedicína * metody MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Reconfiguring the structure and selectivity of existing chemotherapeutics represents an opportunity for developing novel tumor-selective drugs. Here, as a proof-of-concept, the use of high-frequency sound waves is demonstrated to transform the nonselective anthracycline doxorubicin into a tumor selective drug molecule. The transformed drug self-aggregates in water to form ≈200 nm nanodrugs without requiring organic solvents, chemical agents, or surfactants. The nanodrugs preferentially interact with lipid rafts in the mitochondria of cancer cells. The mitochondrial localization of the nanodrugs plays a key role in inducing reactive oxygen species mediated selective death of breast cancer, colorectal carcinoma, ovarian carcinoma, and drug-resistant cell lines. Only marginal cytotoxicity (80-100% cell viability) toward fibroblasts and cardiomyocytes is observed, even after administration of high doses of the nanodrug (25-40 µg mL-1 ). Penetration, cytotoxicity, and selectivity of the nanodrugs in tumor-mimicking tissues are validated by using a 3D coculture of cancer and healthy cells and 3D cell-collagen constructs in a perfusion bioreactor. The nanodrugs exhibit tropism for lung and limited accumulation in the liver and spleen, as suggested by in vivo biodistribution studies. The results highlight the potential of this approach to transform the structure and bioactivity of anticancer drugs and antibiotics bearing sono-active moieties.
- Klíčová slova
- cancer therapy, mitochondria, nanodrugs, ultrasound,
- MeSH
- doxorubicin chemie farmakologie MeSH
- lidé MeSH
- nádory vaječníků * MeSH
- nanočástice * chemie MeSH
- protinádorová antibiotika chemie MeSH
- tkáňová distribuce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- doxorubicin MeSH
- protinádorová antibiotika MeSH
Around half of people with severe COVID-19 requiring intensive care unit (ICU) treatment will survive, but it is unclear how the immune response to SARS-CoV-2 differs between ICU patients that recover and those that do not. We conducted whole-blood immunophenotyping of COVID-19 patients upon admission to ICU and during their treatment and uncovered marked differences in their circulating immune cell subsets. At admission, patients who later succumbed to COVID-19 had significantly lower frequencies of all memory CD8+ T cell subsets, resulting in increased CD4-to-CD8 T cell and neutrophil-to-CD8 T cell ratios. ROC and Kaplan-Meier analyses demonstrated that both CD4-to-CD8 and neutrophil-to-CD8 ratios at admission were strong predictors of in-ICU mortality. Therefore, we propose the use of the CD4-to-CD8 T cell ratio as a marker for the early identification of those individuals likely to require enhanced monitoring and/or pro-active intervention in ICU.
- Klíčová slova
- CD4-to-CD8 ratio, COVID-19, Intensive care unit, SARS-CoV-2, T cells, TEMRA,
- MeSH
- CD4-pozitivní T-lymfocyty imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- COVID-19 imunologie MeSH
- imunofenotypizace metody MeSH
- jednotky intenzivní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- počet lymfocytů metody MeSH
- poměr CD4 a CD8 lymfocytů metody MeSH
- prospektivní studie MeSH
- SARS-CoV-2 imunologie MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
The unmet need for novel therapeutic options for ovarian cancer (OC) deserves further investigation. Among the different novel drugs, small interfering RNAs (siRNAs) are particularly attractive because of their specificity of action and efficacy, as documented in many experimental setups. However, the fragility of these molecules in the biological environment necessitates the use of delivery materials able to protect them and possibly target them to the cancer cells. Among the different delivery materials, those based on polymers and lipids are considered very interesting because of their biocompatibility and ability to carry/deliver siRNAs. Despite these features, polymers and lipids need to be engineered to optimize their delivery properties for OC. In this review, we concentrated on the description of the therapeutic potential of siRNAs and polymer-/lipid-based delivery systems for OC. After a brief description of OC and siRNA features, we summarized the strategies employed to minimize siRNA delivery problems, the targeting strategies to OC, and the preclinical models available. Finally, we discussed the most interesting works published in the last three years about polymer-/lipid-based materials for siRNA delivery.
- Klíčová slova
- delivery, lipid, ovarian cancer, polymer, siRNA,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
