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

Breast cancer is diagnosed through a patient's Breast Self-Examination (BSE), Clinical Breast Examination (CBE), or para-clinical methods. False negativity of PCM in breast cancer diagnostics leads to a persisting problem associated with breast tumors diagnosed only in advanced stages. As the tumor volume/size at which it becomes invasive is not clear, BSE and CBE play an exceedingly important role in the early diagnosis of breast cancer. The quality and effectiveness of BSE and CBE depend on several factors, among which breast stiffness is the most important one. In this study, the authors present four methods for evaluating breast stiffness pathology during mammography examination based on the outputs obtained during the breast compression process, id est, without exposing the patient to X-Ray radiation. Based on the subjective assessment of breast stiffness by experienced medical examiners, a novel breast stiffness classification was designed, and the best method of its objective measurement was calibrated to fit the scale. Hence, this study provides an objective tool for the identification of patients who, being unable to perform valid BSE, could benefit from an increased frequency of mammography screening. Dum vivimus servimus.

• Klíčová slova
• Breast, Breast pathology, Mammography, Novel, Scale, Stiffness,
• MeSH
• časná detekce nádoru * MeSH
• lidé MeSH
• mamografie MeSH
• nádory prsu * diagnóza   MeSH
• plošný screening metody   MeSH
• samovyšetření prsu MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The rapidly growing field of mechanobiology demands for robust and reproducible characterization of cell mechanical properties. Recent achievements in understanding the mechanical regulation of cell fate largely rely on technological platforms capable of probing the mechanical response of living cells and their physico-chemical interaction with the microenvironment. Besides the established family of atomic force microscopy (AFM) based methods, other approaches include optical, magnetic, and acoustic tweezers, as well as sensing substrates that take advantage of biomaterials chemistry and microfabrication techniques. In this review, we introduce the available methods with an emphasis on the most recent advances, and we discuss the challenges associated with their implementation.

• Klíčová slova
• AFM, MEMS, cell mechanics, cell-generated forces, mechanobiology, mechanotransduction, traction force microscopy, tweezing methods,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Fibrosis with excessive amounts of type I collagen is a hallmark of many solid tumours, and fibrosis is a promising target in cancer therapy, but tools for its non-invasive quantification are missing. Here we used magnetic resonance imaging with a gadolinium-based probe targeted to type I collagen (EP-3533) to image and quantify fibrosis in pancreatic ductal adenocarcinoma. An orthotopic syngeneic mouse model resulted in tumours with 2.3-fold higher collagen level compared to healthy pancreas. Animals were scanned at 4.7 T before, during and up to 60 min after i.v. injection of EP-3533, or of its non-binding isomer EP-3612. Ex-vivo quantification of gadolinium showed significantly higher uptake of EP-3533 compared to EP-3612 in tumours, but not in surrounding tissue (blood, muscle). Uptake of EP-3533 visualized in T1-weighted MRI correlated well with spatial distribution of collagen determined by second harmonic generation imaging. Differences in the tumour pharmacokinetic profiles of EP-3533 and EP-3612 were utilized to distinguish specific binding to tumour collagen from non-specific uptake. A model-free pharmacokinetic measurement based on area under the curve was identified as a robust imaging biomarker of fibrosis. Collagen-targeted molecular MRI with EP-3533 represents a new tool for non-invasive visualization and quantification of fibrosis in tumour tissue.

• MeSH
• biologické markery metabolismus   MeSH
• duktální karcinom slinivky břišní metabolismus   patologie   MeSH
• fibróza metabolismus   patologie   MeSH
• gadolinium metabolismus   MeSH
• kolagen metabolismus   MeSH
• kontrastní látky metabolismus   MeSH
• magnetická rezonanční tomografie metody   MeSH
• modely nemocí na zvířatech MeSH
• molekulární zobrazování metody   MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory slinivky břišní metabolismus   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• biologické markery MeSH
• gadolinium MeSH
• kolagen MeSH
• kontrastní látky MeSH