Targeting tumor microenvironment with photodynamic nanomedicine.

Photodynamic therapy (PDT) is approved for the treatment of certain cancers and precancer lesions. While early Photosensitizers (PS) have found their way to the clinic, research in the last two decades has led to the development of third-generation PS, including photodynamic nanomedicine for improved tumor delivery and minimal systemic or phototoxicity. In terms of nanoparticle design for PDT, we are witnessing a shift from passive to active delivery for improved outcomes with reduced PS dosage. Tumor microenvironment (TME) comprises of a complex and dynamic landscape with myriad potential targets for photodynamic nanocarriers that are surface-modified with ligands. Herein, we review ways to improvise PDT by actively targeting nanoparticles (NPs) to intracellular organelles such as mitochondria or lysosomes and so forth, overcoming the limitations caused by PDT-induced hypoxia, disrupting the blood vascular networks in tumor tissues-vascular targeted PDT (VTP) and targeting immune cells for photoimmunotherapy. We propose that a synergistic outlook will help to address challenges such as deep-seated tumors, metastasis, or relapse and would lead to robust PDT response in patients.

The Influence of COVID-19 on Patient Mobilization and Injury Attributes in the ICU: A Retrospective Analysis of a Level II Trauma Center.

The objectives of this study were to determine the effect of COVID-19 on physical therapy (PT) mobilization of trauma patients and to determine if mobilization affected patient course in the ICU. This retrospective study included patients who were admitted to the ICU of a level II trauma center. The patients were divided into two groups, i.e., those admitted before (n = 378) and after (n = 499) 1 April 2020 when Georgia's COVID-19 shelter-in-place order was mandated. The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. A secondary analysis focused specifically on the after-COVID patients examined the extent to which mobilization (n = 328) or lack of mobilization (n = 171) influenced ICU outcomes (e.g., mortality, readmission). The two groups were contrasted on nominal and ratio variables using Chi-square and Student's t-tests. The after-COVID patients had higher injury severity as a greater proportion was classified as severely injured (i.e., >15 on Injury Severity Score) compared to the before-COVID patients. After-COVID patients also had a greater cumulative number of comorbidities and experienced greater complications in the ICU. Despite this, there was no difference between patients in receiving a PT consultation or days to mobilization. Within the after-COVID cohort, those who were mobilized were older, had greater Glasgow Coma Scale scores, had longer total hospital days, and had a lesser mortality rate, and a higher proportion were female. Despite shifting patient injury attributes post-COVID-19, a communicable disease, mobilization care remained consistent and effective.

Mechanistic insights into nanoparticle surface-bacterial membrane interactions in overcoming antibiotic resistance.

Antimicrobial Resistance (AMR) raises a serious concern as it contributes to the global mortality by 5 million deaths per year. The overall impact pertaining to significant membrane changes, through broad spectrum drugs have rendered the bacteria resistant over the years. The economic expenditure due to increasing drug resistance poses a global burden on healthcare community and must be dealt with immediate effect. Nanoparticles (NP) have demonstrated inherent therapeutic potential or can serve as nanocarriers of antibiotics against multidrug resistant (MDR) pathogens. These carriers can mask the antibiotics and help evade the resistance mechanism of the bacteria. The targeted delivery can be fine-tuned through surface functionalization of Nanocarriers using aptamers, antibodies etc. This review covers various molecular mechanisms acquired by resistant bacteria towards membrane modification. Mechanistic insight on 'NP surface-bacterial membrane' interactions are crucial in deciding the role of NP as therapeutic. Finally, we highlight the potential accessible membrane targets for designing smart surface-functionalized nanocarriers which can act as bacteria-targeted robots over the existing clinically available antibiotics. As the bacterial strains around us continue to evolve into resistant versions, nanomedicine can offer promising and alternative tools in overcoming AMR.