J.Q. Ho

Tumor-associated macrophages, nanomedicine and imaging: the axis of success in the future of cancer immunotherapy

The success of any given cancer immunotherapy relies on several key factors. In particular, success hinges on the ability to stimulate the immune system in a controlled and precise fashion, select the best treatment options and appropriate therapeutic agents, and use highly effective tools to accurately and efficiently assess the outcome of the immunotherapeutic intervention. Furthermore, a deep understanding and effective utilization of tumor-associated macrophages (TAMs), nanomedicine and biomedical imaging must be harmonized to improve treatment efficacy. Additionally, a keen appreciation of the dynamic interplay that occurs between immune cells and the tumor microenvironment (TME) is also essential. New advances toward the modulation of the immune TME have led to many novel translational research approaches focusing on the targeting of TAMs, enhanced drug and nucleic acid delivery, and the development of theranostic probes and nanoparticles for clinical trials. In this review, we discuss the key cogitations that influence TME, TAM modulations and immunotherapy in solid tumors as well as the methods and resources of tracking the tumor response. The vast array of current nanomedicine technologies can be readily modified to modulate immune function, target specific cell types, deliver therapeutic payloads and be monitored using several different imaging modalities. This allows for the development of more effective treatments, which can be specifically designed for particular types of cancer or on an individual basis. Our current capacities have allowed for greater use of theranostic probes and multimodal imaging strategies that have led to better image contrast, real-time imaging capabilities leveraging targeting moieties, tracer kinetics and enabling more detailed response profiles at the cellular and molecular levels. These novel capabilities along with new discoveries in cancer biology should drive innovation for improved biomarkers for efficient and individualized cancer therapy.

Spiritual Care in the Intensive Care Unit: A Narrative Review:

Spiritual care is an important component of high-quality health care, especially for critically ill patients and their families. Despite evidence of benefits from spiritual care, physicians and other health-care providers commonly fail to assess and address their patients’ spiritual care needs in the intensive care unit (ICU). In addition, it is common that spiritual care resources that can improve both patient outcomes and family member experiences are underutilized. In this review, we provide an overview of spiritual care and its role in the ICU. We review evidence demonstrating the benefits of, and persistent unmet needs for, spiritual care services, as well as the current state of spiritual care delivery in the ICU setting. Furthermore, we outline tools and strategies intensivists and other critical care medicine health-care professionals can employ to support the spiritual well-being of patients and families, with a special focus on chaplaincy services.

Comment on “Early Innovative Immersion: A Course for Pre-Medical Professions Students Using Point-of-Care Ultrasound”: Clinical Letters

this may eliminate artifacts and allow accurate measurement of ONSD. In addition, calculation packages may lead to automated ONSD measurements in the future, which could potentially eliminate interobserver variability. We agree with the authors that enlarged ONSDs are not always suggestive of intracranial hypertension, and in fact discussed numerous applications for ONSD measurements in our manuscript: “Ultrasound measurement of the optic nerve sheath diameter (ONSD) has been shown to be a useful tool in the assessment of ICP and . . . high altitude mountain sickness, idiopathic intracranial hypertension, acute head injury and preeclampsia.” Finally, the 30-degree test described by the Iaconetta et al is very interesting and should be further evaluated in the acute setting. Although it may show promise, we feel that ONSD measurements in the acute setting can be difficult to execute properly, as patients with acute illnesses often have barriers to examinations such as being paralyzed, medically sedated, or presenting with altered mental status.

Chapter 4 – Nanocytotoxicity

The ability to assess cellular cytotoxicity is a critically important element to the development and use of nanoparticles. This is especially true as cell viability assays represent the beginning of the preclinical pipeline. A number of dependable approaches exist to investigate possible toxic effects resulting from iron oxide nanoparticles and leveraging mechanisms including membrane integrity, metabolic function, redox, and inflammation. These methods use dyes and other agents to produce easily quantifiable readouts employing light microcopy, fluorescence, colorimetric, and other techniques. The broad range of approaches available allow for any nanoparticle to be quickly characterized for toxicity in the cell type of choice. In this section, we discuss the various established methods for characterizing nanocytotoxicity.

Chapter 11 – Cancer Therapy

Over the last two decades, iron oxide nanoparticles have demonstrated great progress and potential for use in oncological medicine. Due to their overall utility for a vast number of applications, iron oxides have been extensively investigated. This type of nanoparticle has numerous desirable properties such as facile synthesis, ease of functionalization, favorable magnetic characteristics, and biocompatible and biodegradable and is generally considered safe. Cancer therapy has already benefited in a number areas from the use of iron oxide nanoparticles in such areas as cancer imaging, a variety of therapeutic approaches including immunotherapy, cell tracking and monitoring, improved efficacy, and safety. While several forms of magnetite-based nanoparticle formulations are FDA approved as either magnetic resonance imaging (MRI) contrast agents or iron-deficiency therapeutics, there are still a number of other applications that these nanoparticles can be used for. Iron oxide nanoparticles can come in a number of shapes, sizes, and composition and can have modifiable coatings with targeting molecules such as antibodies, peptides, and small molecules. These surface moieties can improve tumor-targeting capabilities, while the nanoparticle itself can allow for monitoring by MRI and even optical methods depending on the modifications used and intended applications. Other potential cancer applications include improved delivery of cancer therapeutics, magnetic hypothermia, photothermal ablation, personalized medicine approaches, and photodynamic therapy. These approaches can result in multifunctional and/or theranostic nanoparticles suitable for diagnosis, treatment, and treatment monitoring of cancer.

Chapter 9 – Drug Delivery

Iron oxide nanoparticles have been approved for many biomedical applications, because of their ultrafine size, biocompatibility, and superparamagnetic properties. Superparamagnetic iron oxide nanoparticles (SPIONs), in conjunction with external magnetic fields, enable particles to be delivered to the desired target site and keep them at the site during drug release to act locally. Therefore, this combination decreases the medication dosage and minimizes the drugs systemic effect. The potential for SPION applications has grown substantially in recent years. Following new advancements, these nanoparticles have been extensively used as delivery systems for drugs, genes, and radionuclides in clinical medicine. Here, we discuss the role of iron oxide nanoparticles in drug delivery and passive and active drug targeting systems.

Chapter 10 – Tumor-Targeted Therapy

Abstract With the increase in cancer incidences, developments of precise diagnostic and therapeutic methods have gained further significance. Iron oxide nanoparticles have been used as targeted cancer therapy agents and contrast enhancement agents for targeted cancer diagnosis. In this chapter, we discuss the applications of iron oxide nanoparticles for targeted tumor therapy and as multimodal imaging contrast agents.

Chapter 5 – Magnetic Particle Imaging (MPI)

Abstract Magnetic particle imaging (MPI) is a novel radiation-free and highly sensitive imaging modality that directly maps magnetic nanoparticles. Unlike common imaging modalities, MPI introduces the potential to tackle the challenges of tracking contrast agents or tracers directly in vivo. Up to now, the synthesis of multiple metallic and alloy magnetic nanoparticles has been reported. Among them, superparamagnetic iron oxide nanoparticles (SPIONs) have been used in various biomedical applications including diagnostics, imaging, targeting, and therapy due to their suitable magnetic properties and biocompatibility. SPIONs are highly biocompatible and uniquely suitable for in vivo biomedical applications. Here, we discuss the biomedical applications of iron oxide nanoparticles using MPI.