Biology subjects

Cihova, M.

Publications and source records attributed to Cihova, M..

3 recordsLinked to original sources

bioRxiv2026

An injectable soft implant for long-acting, reversible, ultra-stable release of therapeutics

Providing long-term (>6 months) zero-order drug release from easily administered formulations is a key challenge in improving patient adherence and facilitating access. Herein, we report the design and development of an injectable, biodegradable, long-acting polymeric microparticle-embedded hydrogel platform for prolonged, zero-order release of therapeutics. This "soft implant" is injectable for ease of administration and can be retrieved via a small incision, allowing for discontinuation of therapy if desired. Central to the platform are surface-eroding poly(orthoester) (POE) microparticles, which were molecularly tailored to tune zero-order drug release across a wide range of timeframes. We demonstrate the clinical potential of the "soft implant" using levonorgestrel, a contraceptive agent requiring sustained dosing. In vitro, we observed zero-order release for 300 days, projected for >12 months, with behavior consistent with surface erosion further supported through Raman chemical mapping. In vivo studies confirmed zero-order release for six months, projected to 12 months, from a subcutaneous injection in rats. We envision that our platform could transform therapies that require long-term, regular drug dosing, significantly improving compliance and therapy outcomes.

bioengineering↗

bioRxiv2025

Anti-amyloid antibody effects on Aβ-42 protein aggregates profiled using nanospectroscopy

Anti-amyloid beta (A{beta}) drugs such as aducanumab and lecanemab are designed to clear brain amyloids and slow Alzheimers disease (AD) progression. While immunoassays provide ensemble-level details on anti-A{beta} drug interactions with protein targets, their interfacial effects are largely unknown at a single-particle level. Here, we profile untreated and aducanumab-treated A{beta}-42 protein aggregates from oligomers to fibrils using atomic force microscopy coupled with infrared spectroscopy (nanospectroscopy). Based on the recorded morphological and secondary structure details of aducanumab-treated A{beta}-42 aggregates using nanospectroscopy, we observed a reduction in oligomer prevalence and formation of larger diameter fibril bundles compared to identically prepared untreated-A{beta}-42 peptides. Conversely, controls based on lecanemab did not reveal any quenching of the A{beta}-42 oligomer generation. Moreover, lecanemab was evidenced to bind along the full length of the A{beta}-42 protofibril surface preferentially. Importantly, the structure of A{beta}-42 fibrils did not disassemble in both studies upon the adsorption of aducanumab and lecanemab. Additional experiments were also conducted, such as aggregation kinetic assays and Fourier transform infrared spectroscopy on aducanumab and lecanemab-treated A{beta}-42 protein aggregates that corroborated the findings from nanospectroscopy studies. Our work highlights the usefulness of nanospectroscopy in studying elemental anti-amyloid antibody interactions with protein biomarkers, a requisite for improving Alzheimers disease-modifying treatments.

biophysics↗

bioRxiv2025

Development of Paclitaxel Resistance in Triple-Negative Breast Cancer Is Associated with Extensive DNA Methylation Changes That Are Partially Reversed by Decitabine

AimsChemotherapy resistance remains a major challenge in breast cancer (BC) treatment. This study investigated whether resistance development is associated with DNA methylation changes and assessed the potential of the DNA methyltransferase inhibitor decitabine (DAC) to reverse these alterations and enhance chemosensitivity. MethodsMolecular profiling and functional assays were used to characterize paclitaxel-(PAC) and doxorubicin-(DOX) resistant BC cell lines derived from luminal A (T-47D), triple-negative (MDA-MB-231), and HER2-positive trastuzumab-resistant (JIMT-1) models. Therapeutic responses to DAC and DOX, alone and in combination, were evaluated in MDA-MB-231 xenografts. DNA methylation-associated gene expression changes were analyzed through integrative approaches. ResultsChemoresistant cells exhibited a slow-cycling phenotype, reduced tumorigenicity, and extensive genomic alterations. Upregulation of RELB and downregulation of PPARG were observed across several resistant cell lines, while CDA expression was uniformly elevated in all DOX-resistant models. PAC-resistant xenografts displayed widespread methylation and transcriptomic reprogramming. DAC treatment partially restored aberrant methylation patterns and increased Ki-67 expression, potentially enhancing DOX responsiveness. ConclusionsChemoresistance in BC involves extensive genomic and epigenetic reprogramming. DAC modulates methylation and tumor phenotype but is insufficient to overcome resistance, highlighting the need for rational combination strategies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/655519v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@8c6b06org.highwire.dtl.DTLVardef@c67805org.highwire.dtl.DTLVardef@1f1b282org.highwire.dtl.DTLVardef@feb046_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗