Circulating tumor cells reveal early predictors of disease progression in patients with stage III NSCLC undergoing chemoradiation and immunotherapy.

Circulating tumor cells (CTCs) are early signs of metastasis and can be used to monitor disease progression well before radiological detection by imaging. Using an ultrasensitive graphene oxide microfluidic chip nanotechnology built with graphene oxide sheets, we were able to demonstrate that CTCs can be specifically isolated and molecularly characterized to predict future progression in patients with stage III non-small cell lung cancer (NSCLC). We analyzed CTCs from 26 patients at six time points throughout the treatment course of chemoradiation followed by immune checkpoint inhibitor immunotherapy. We observed that CTCs decreased significantly during treatment, where a larger decrease in CTCs predicted a significantly longer progression-free survival time. Durvalumab-treated patients who have future progression were observed to have sustained higher programmed death ligand 1+ CTCs compared to stable patients. Gene expression profiling revealed phenotypically aggressive CTCs during chemoradiation. By using emerging innovative bioengineering approaches, we successfully show that CTCs are potential biomarkers to monitor and predict patient outcomes in patients with stage III NSCLC.

Emerging micro-nanotechnologies for extracellular vesicles in immuno-oncology: from target specific isolations to immunomodulation.

Extracellular vesicles (EVs) have been hypothesized to incorporate a variety of crucial roles ranging from intercellular communication to tumor pathogenesis to cancer immunotherapy capabilities. Traditional EV isolation and characterization techniques cannot accurately and with specificity isolate subgroups of EVs, such as tumor-derived extracellular vesicles (TEVs) and immune-cell derived EVs, and are plagued with burdensome steps. To address these pivotal issues, multiplex microfluidic EV isolation/characterization and on-chip EV engineering may be imperative towards developing the next-generation EV-based immunotherapeutics. Henceforth, our aim is to expound the state of the art in EV isolation/characterization techniques and their limitations. Additionally, we seek to elucidate current work on total analytical system based technologies for simultaneous isolation and characterization and to summarize the immunogenic capabilities of EV subgroups, both innate and adaptive. In this review, we discuss recent state-of-art microfluidic/micro-nanotechnology based EV screening methods and EV engineering methods towards therapeutic use of EVs in immune-oncology. By venturing in this field of EV screening and immunotherapies, it is envisioned that transition into clinical settings can become less convoluted for clinicians.

Electrochemical Strategy for Eradicating Fluconazole-Tolerant Candida albicans Using Implantable Titanium.

A persistent problem in modern health care derives from the overwhelming presence of antibiotic-resistant microbes on biomaterials, more specifically, fungal growth on metal-based implants. This study seeks to investigate the antifungal properties of low-level electrochemical treatments delivered using titanium electrodes against Candida albicans. We show that C. albicans can be readily controlled with electrical currents/potentials, reducing the number of viable planktonic cells by 99.7% and biofilm cells by 96.0-99.99%. Additionally, this study explores the ability of the electrochemical treatments to potentiate fluconazole, a clinically used antifungal drug. We have found that electrochemical treatment substantially enhances fluconazole killing activity. While fluconazole alone exhibits a low efficiency against the stationary phase and biofilm cells of C. albicans, complete eradication corresponding to 7-log killing is achieved when the antifungal drug is provided subsequently to the electrochemical treatment. Further mechanistic analyses have revealed that the sequential treatment shows a complex multimodal action, including the disruption of cell wall integrity and permeability, impaired metabolic functions, and enhanced susceptibility to fluconazole, while altering the biofilm structure. Altogether, we have developed and optimized a new therapeutic strategy to sensitize and facilitate the eradication of fluconazole-tolerant microbes from implantable materials. This work is expected to help advance the use of electrochemical approaches in the treatment of infections caused by C. albicans in both nosocomial and clinical cases.