A Self-Assembly ICG Nanoparticle Potentiating Targeted Photothermal and Photodynamic Therapy in NSCLC.

In nonsmall cell lung cancers (NSCLC), near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has proven to be an efficient approach for locating pulmonary nodules and pulmonary sentinel lymph nodes. However, due to a lack of tumor selectivity, ICG's use as a photosensitizer for photothermal therapy (PTT) and photodynamic therapy (PDT) is restricted. In the current study, we aimed to develop a type of high-performance NIR nanoparticle formulated with ICG to enhance its targeted efficacy and tumor specificity on NSCLC. An ICG-osimertinib nanoparticle (ICG-Osi) was self-assembled through π-π stacking, with a size of 276 nm and a surface charge of -7.4 mV. The NIR visibility and epidermal growth factor receptor (EGFR) targetability of the ICG-Osi was confirmed by its binding efficiency to EGFR-expressing NSCLC cells in vitro and in vivo, regardless of EGFR mutation status. The targeted effect was further confirmed in mouse xenograft models and showed an extended tumor retention time (>96 h). We demonstrated a significantly enhanced hyperthermia effect and a retained reactive oxygen species (ROS) generating ability of ICG-Osi, resulting in a 2-fold higher cell death rate than ICG alone. The ICG-Osi down-regulated GPX4 and p62 expression while up-regulating caspase-3 and beclin1 expression in NSCLC cells, indicating a complex network of cell death-related proteins. Considering the merits of simple assembly, EGFR binding efficacy, improved hyperthermia effect, and efficient cancer cell suppression, the ICG-Osi exhibits great potential for clinical application in EGFR-expressing NSCLC therapy.

Follow-Ups on Persistent Symptoms and Pulmonary Function Among Post-Acute COVID-19 Patients: A Systematic Review and Meta-Analysis.

Objective: As the number of recovering COVID-19 patients increases worldwide, the persistence of symptoms and signs through the post-acute phase indicates an urgent need for prolonged follow-up care. To explore existing data about post-acute COVID-19 syndrome, this meta-analysis assesses the prevalence of persistent manifestations in multiple systems and abnormalities in lung function, as well as their related risks in patients with various severities. Methods: Articles about discharged COVID-19 patients (published from January 1, 2020 to February 23, 2021) were obtained by searching four databases. Cohort studies with follow-up periods >1 month post-discharge or >2 months post-admission were included. Results: A total of 4,478 COVID-19 patients from 16 cohort studies were included in this meta-analysis. Fatigue or weakness (47%) were the most prevalent physical effects of post-acute COVID-19 syndrome, while psychosocial (28%) symptoms were the most common manifestations among several systems. Abnormalities in lung function of recovering patients, i.e., DLCO <80% (47%, 95% CI: 32-61%) persisted for long periods. Severe patients were more likely to present joint pain (OR 1.84, 95% CI: 1.11-3.04) and decreased lung functions compared with non-severe patients, with pooled ORs for abnormal TLC, FEV1, FVC, and DLCO of 3.05 (95% CI: 1.88-4.96), 2.72 (95% CI: 1.31-5.63), 2.52 (95% CI: 1.28-4.98), and 1.82 (95% CI: 1.32-2.50), respectively. Conclusions: Our research indicates that patients recovering from COVID-19 manifest long-term, multi-system symptoms, and the adverse effects on psychosocial health and lung functions were the most extensive and persistent. These findings together may facilitate much needed in-depth study of clinical treatments for long-term, post-acute phase symptoms that affect a great number of recovering COVID-19 patients.