RESUMEN
Cu-BTC framework has received a considerable attention in recent years as a drug carrier candidate for cancer treatment due to its unique structural properties and promising biocompatibility. However, its intrinsic deficiency for medical imaging potentially limits its bioapplications; To address this subject, a magnetic nano/microscale MOF has been successfully fabricated by introducing Fe3O4 nanoparticles as an imaging agent into the porous isoreticular MOF [Cu3(BTC)2] as a drug carrier. The synthesized magnetic MOFs exhibits a high loading capacity (40.5%) toward the model anticancer DOX with an excellent pH-responsive drug release. The proposed nanocomposite not only possesses large surface area, high magnetic response, large mesopore volume, high transverse relaxivity (r 2) and good stability but also exhibits superior biocompatibility, specific tumor cellular uptake, and significant cancer cell viability inhibitory effect without any targeting agent. It is expected that the synthesized magnetic nano/microcomposite may be used for clinical purposes and can also serve as a platform for photoactive antibacterial therapy ae well as pH/GSH/photo-triple-responsive nanocarrier.
RESUMEN
INTRODUCTION: The information derived from the number and characteristics of circulating tumor cells (CTCs), is crucial to ensure appropriate cancer treatment monitoring. Currently, diverse microfluidic platforms have been developed for isolating CTCs from blood, but it remains a challenge to develop a low-cost, practical, and efficient strategy. OBJECTIVES: This study aimed to isolate CTCs from the blood of cancer patients via introducing a new and efficient micropillar array-based microfluidic chip (MPA-Chip), as well as providing prognostic information and monitoring the treatment efficacy in cancer patients. METHODS: We fabricated a microfluidic chip (MPA-Chip) containing arrays of micropillars with different geometries (lozenge, rectangle, circle, and triangle). We conducted numerical simulations to compare velocity and pressure profiles inside the micropillar arrays. Also, we experimentally evaluated the capture efficiency and purity of the geometries using breast and prostate cancer cell lines as well as a blood sample. Moreover, the device's performance was validated on 12 patients with breast cancer (BC) in different states. RESULTS: The lozenge geometry was selected as the most effective and optimized micropillar design for CTCs isolation, providing high capture efficiency (>85 %), purity (>90 %), and viability (97 %). Furthermore, the lozenge MPA-chip was successfully validated by the detection of CTCs from 12 breast cancer (BC) patients, with non-metastatic (median number of 6 CTCs) and metastatic (median number of 25 CTCs) diseases, showing different prognoses. Also, increasing the chemotherapy period resulted in a decrease in the number of captured CTCs from 23 to 7 for the metastatic patient. The MPA-Chip size was only 0.25 cm2 and the throughput of a single chip was 0.5 ml/h, which can be increased by multiple MPA-Chips in parallel. CONCLUSION: The lozenge MPA-Chip presented a novel micropillar geometry for on-chip CTC isolation, detection, and staining, and in the future, the possibilities can be extended to the culture of the CTCs.
Asunto(s)
Neoplasias de la Mama , Células Neoplásicas Circulantes , Masculino , Humanos , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patología , Microfluídica/métodos , Separación Celular/métodos , Línea Celular TumoralRESUMEN
Separation and detection of cells and particles in a suspension are essential for various applications, including biomedical investigations and clinical diagnostics. Microfluidics realizes the miniaturization of analytical devices by controlling the motion of a small volume of fluids in microchannels and microchambers. Accordingly, microfluidic devices have been widely used in particle/cell manipulation processes. Different microfluidic methods for particle separation include dielectrophoretic, magnetic, optical, acoustic, hydrodynamic, and chemical techniques. Dielectrophoresis (DEP) is a method for manipulating polarizable particles' trajectories in non-uniform electric fields using unique dielectric characteristics. It provides several advantages for dealing with neutral bioparticles owing to its sensitivity, selectivity, and noninvasive nature. This review provides a detailed study on the signal-based DEP methods that use the applied signal parameters, including frequency, amplitude, phase, and shape for cell/particle separation and manipulation. Rather than employing complex channels or time-consuming fabrication procedures, these methods realize sorting and detecting the cells/particles by modifying the signal parameters while using a relatively simple device. In addition, these methods can significantly impact clinical diagnostics by making low-cost and rapid separation possible. We conclude the review by discussing the technical and biological challenges of DEP techniques and providing future perspectives in this field.