RESUMO
Timely identification of cancers is pivotal in optimizing treatment efficacy and reducing their widespread impact. This study introduces a novel biosensor for the sensitive electrochemical detection of cancer cells overexpressing mucin 1 (MUC1), a well-established model for breast cancer. The sensor substrate comprises gold columnar nanostructures obtained through glancing angle deposition (GLAD) of copper nanostructures, subsequently replaced by gold via a facile galvanic replacement process. Functionalizing these gold nanostructures with aptamers targeting the MUC1 glycoproteins, a prominent cancer biomarker, enables specific recognition of MCF-7 breast cancer cells. The proposed electrochemical sensing platform offers several advantages, including high selectivity, a wide linear range of detection, a low detection limit of 30 cells per mL, and long-term stability, rendering this sensor highly desirable for definitive breast cancer diagnosis.
Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , Técnicas Eletroquímicas , Ouro , Mucina-1 , Humanos , Técnicas Biossensoriais/métodos , Ouro/química , Células MCF-7 , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Mucina-1/análise , Mucina-1/metabolismo , Feminino , Nanoestruturas/química , Nanopartículas Metálicas/química , Aptâmeros de Nucleotídeos/químicaRESUMO
Double-layer dermal substitutes (DS) generally provide more effective therapeutic outcomes than single-layer substitutes. The architectural design of DS incorporates an outer layer to protect against bacterial invasions and maintain wound hydration, thereby reducing the risk of infection and the frequency of dressing changes. Moreover, the outer layer is a mechanical support for the wound, preventing undue tension in the affected area. A 3D-printed polycaprolactone (PCL) membrane was utilized as the outer layer to fabricate DS wound dressing. Simultaneously, a polyvinyl alcohol/chitosan/sildenafil citrate (PVA/CS/SC) scaffold was electrospun onto the PCL membrane to facilitate cellular adhesion and proliferation. Scanning electron microscopy (SEM) analysis of the PCL filaments revealed a consistent cross-sectional surface and structure, with an average diameter of 562.72⯱â¯29.15⯵m. SEM results also demonstrated uniform morphology and beadless structure for the PVA/CS/SC scaffold, with an average fiber diameter of 366.77⯱â¯1.81â¯nm for PVA/CS. The addition of SC led to an increase in fiber diameter while resulting in a reduction in tensile strength. However, drug release analysis indicated that the SC release from the sample can last up to 72â¯h. Animal experimentation confirmed that DS wound dressing positively accelerated wound closure and collagen deposition in the Wistar rat skin wound model.
Assuntos
Bandagens , Quitosana , Poliésteres , Álcool de Polivinil , Impressão Tridimensional , Citrato de Sildenafila , Cicatrização , Quitosana/química , Quitosana/farmacologia , Álcool de Polivinil/química , Animais , Poliésteres/química , Cicatrização/efeitos dos fármacos , Ratos , Citrato de Sildenafila/farmacologia , Citrato de Sildenafila/química , Membranas Artificiais , Masculino , Alicerces Teciduais/química , Liberação Controlada de Fármacos , Resistência à TraçãoRESUMO
This study introduces an innovative co-delivery approach using the MCM-co-polymerized nanosystem, integrating chitosan and polyethylene glycol, and targeted by the MUC-1 aptamer (MCM@CS@PEG-APT). This system enables simultaneous delivery of the GFP plasmid and doxorubicin (DOX). The synthesis of the nanosystem was thoroughly characterized at each step, including FTIR, XRD, BET, DLS, FE-SEM, and HRTEM analyses. The impact of individual polymers (chitosan and PEG) on payload retardation was compared to the co-polymerized MCM@CS@PEG conjugation. Furthermore, the DOX release mechanism was investigated using various kinetic models. The nanosystem's potential for delivering GFP plasmid and DOX separately and simultaneously was assessed through fluorescence microscopy and flow cytometry. The co-polymerized nanosystem exhibited superior payload entrapment (1:100 ratio of Plasmid:NPs) compared to separately polymer-coated counterparts (1:640 ratio of Plasmid:NPs). Besides, the presence of pH-sensitive chitosan creates a smart nanosystem for efficient DOX and GFP plasmid delivery into tumor cells, along with a Higuchi model pattern for drug release. Toxicity assessments against breast tumor cells also indicated reduced off-target effects compared to pure DOX, introducing it as a promising candidate for targeted cancer therapy. Cellular uptake findings demonstrated the nanosystem's ability to deliver GFP plasmid and DOX separately into MCF-7 cells, with rates of 32% and 98%, respectively. Flow cytometry results confirmed efficient co-delivery, with 42.7% of cells showing the presence of both GFP-plasmid and DOX, while 52.2% exclusively contained DOX. Overall, our study explores the co-delivery potential of the MCM@CS@PEG-APT nanosystem in breast cancer therapy. This system's ability to co-deliver multiple agents preciselyopens new avenues for targeted therapeutic strategies.
Assuntos
Neoplasias da Mama , Quitosana , Nanopartículas , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Polimerização , Doxorrubicina/farmacologia , Oligonucleotídeos , Plasmídeos , DNA , Sistemas de Liberação de Medicamentos/métodos , Portadores de FármacosRESUMO
This study is focused on the importance of nanohydroxyapatite (nHA) particle morphology with the same particle size range on the rheological behavior of polycaprolactone (PCL) composite ink with nHA as a promising candidate for additive manufacturing technologies. Two different physiologic-like nHA morphologies, that is, plate and rod shape, with particles size less than 100 nm were used. nHA powders were well characterized and the printing inks were prepared by adding the different ratios of nHA powders to 50% w/v of PCL solution (nHA/PCL: 35/65, 45/55, 55/45, and 65/35 w/w%). Subsequently, the influence of nHA particle morphology and concentration on the printability and rheological properties of composite inks was investigated. HA nanopowder analysis revealed significant differences in their microstructural properties, which affected remarkably the composite ink printability in several ways. For instance, adding up to 65% w/w of plate-like nHA to the PCL solution was possible, while nanorod HA could not be added above 45% w/w. The printed constructs were successfully fabricated using the extrusion-based printing method and had a porous structure with interconnected pores. Total porosity and surface area increased with nHA content due to the improved fiber stability following deposition of material ink. Consequently, degradation rate and bioactivity increased, while compressive properties decreased. While nanorod HA particles had a more significant impact on the mechanical strength than plate-like morphology, the latter showed less crystalline order, which makes them more bioactive than nanorod HA. It is therefore important to note that the nHA microstructure broadly affects the printability of printing ink and should be considered according to the intended biomedical applications.