The devastating nature of cancer continues to be one of the leading causes of death in the world. Chemotherapy is among the most common forms of cancer treatment but comes with a host of adverse effects caused by the therapeutic agents damaging healthy tissue and organs. To limit these side effects, scientists have been designing stimuli responsive drug delivery vessels for targeted release. This Review focuses on the incorporation of stimuli responsive linkages in targeted drug delivery systems to enhance therapeutic efficiency. These platforms are primarily employed to control the distribution of anticancer agents in the body to reduce the adverse side effects caused by their toxicities. We will outline how drug delivery vessels are constructed so that exposure to select environmental and external stimuli releases the enclosed drug only at the target site. Stimuli responsive components are integrated within drug delivery vessels in the form of cross-linkers, polymers, and surface modifications. The changes, these moieties undergo upon stimuli exposure, cascade into larger scale alterations to the platforms, resulting in complete disassembly, reversible morphological variations, and enhanced cellular uptake. The ability for these modes of delivery to be initiated exclusively under stimuli exposure allows for release of toxic therapeutic agents to be confined only to the affected area.
Theranostics is a fast-growing field due to demands for new, efficient therapeutics which could be precisely delivered to the target site using multimodal imaging with enhancing auxiliary actions. In this review article we discuss theranostic nanoplatforms containing polymers and magnetic nanoparticles along with other components. Magnetic nanoparticles allow for both diagnostic and therapeutic (hyperthermia) capabilities, while polymers can be reservoirs for drugs and are easily functionalized for cell targeting. We focus on the most important design strategies to achieve optimal theranostic effects as well as the roles of different components included in theranostics, reviewing the literature from the last 5 years.
Background Point of care ultrasound (PoCUS) is a diagnostic tool that can efficiently answer targeted clinical questions at the bedside. Such questions include confirming or ruling out the presence of a specific complication suspected by the clinician, like an abdominal aortic aneurysm, for example. Proper identification of any such complication is reliant upon a fundamental knowledge and recognition of normal anatomy in each view, so the ultrasound provider can distinguish normal from a variety of hallmark pathologic signs. A positive finding warrants immediate changes in management, often including further imaging to guide interventions. However, indeterminate, or incidental findings unrelated to the patient’s chief complaint can be found. While usually benign, sometimes these findings are indicative of an underlying pathology not initially suspected by the physician. In these settings, PoCUS has limited diagnostic value, and therefore it is important to highlight the need for further imaging following discovery of abnormal or incidental findings on an ultrasound exam. Case The patient was a 75-year-old female with COPD, coronary artery disease and hypertension. Her overall health declined after an admission for COVID pneumonia, which required treatment for oxygen. She never improved completely and was diagnosed with pulmonary fibrosis, likely secondary to COVID-19. She presented to our outpatient clinic for follow up from a recent hospitalization for respiratory decompensation and heart failure. During the visit she complained of intermittent right sided abdominal pain which had been present for a couple weeks. It was not associated with eating, and the pain did improve some after passing gas. The decision was made to perform a bedside ultrasound of her gallbladder to look for gallstones. Upon visualizing her gallbladder, hyperechoic shadowing in a smooth, circumferential nature filled the gallbladder. The differential included porceline gallbladder, stone filled gallbladder, or emphysematous cholecystitis. She was referred for further imaging, but before she could get imaging completed, she presented to the emergency department due to worsening pain. A CT scan of the abdomen showed an ill-defined soft tissue mass with surrounding inflammation involving the inferior right hepatic lobe, gallbladder and cecal visualization. Overall, given the surrounding inflammation this was favored to represent perforated cholecystitis with inflammatory fistula. Interventional radiology attempted to place a drain which was unsuccessful but did demonstrate fistulization with the colon. She later had a cholecystectomy performed, with a pathology report which detailed results showing metastatic poorly differentiated adenocarcinoma with signet ring and mucinous features. Oncology was consulted for treatment options, but unfortunately the patient passed away from cardiopulmonary compromise before treatment could be initiated. Conclusion This case demonstrates the importance of follow up imaging for abnormal bedside ultrasound studies which do not follow the typical PoCUS pathway. Point of care ultrasound is used to answer a binary question, “Does my patient have a gallstone?” for example. If there are abnormal findings, or findings which do not correlate with the history and physical examination, more advanced imaging assessment is required and should be ordered by the point of care ultrasound provider.
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