ABSTRACT
Melanoma is a form of skin cancer with an increased ability to metastasis to organs such as the brain and other visceral organs, contributing to its aggressiveness and seriousness. Melanoma's prevalence around the globe rapidly continues to rise. Melanoma development is a complex process often depicted as a step-wise process with the potential to end in metastatic disease. Recent studies suggest that the process could be non-linear. Melanoma has many risk factors including genetics, UV exposure, or exposure to carcinogens. Current treatments for metastatic melanoma include surgery, chemotherapy, and immune checkpoint inhibitors (ICIs); however, each of these treatments comes with limitations, toxicities, and relatively poor outcomes. There are various guidelines set by the American Joint Committee on Cancer guiding surgical treatment options based on the site of metastasis. Surgical treatments cannot fully treat widespread metastatic melanoma but can contribute to better patient outcomes overall. Many chemotherapy options are ineffective against melanoma or come with extreme toxicities; however, alkylating agents, platinum analogs, and microtubular toxins have shown some effectiveness against metastatic melanoma. ICIs are a relatively new treatment option and offer a promising option for patients; however, ICIs are subject to tumor resistance mechanisms and are not effective for every metastatic melanoma patient. Due to the limitations of conventional treatments, there is a need for newer and more effective treatment options for metastatic melanoma. This review aims to highlight the current surgical, chemotherapy, and ICI treatments for metastatic melanoma, as well as current clinical and preclinical investigations to discover revolutionary options for patients.
ABSTRACT
Nanoparticles are a promising approach for improving intra-articular drug delivery and tissue targeting. However, techniques to non-invasively track and quantify their concentration in vivo are limited, resulting in an inadequate understanding of their retention, clearance, and biodistribution in the joint. Currently, fluorescence imaging is often used to track nanoparticle fate in animal models; however, this approach has limitations that impede long-term quantitative assessment of nanoparticles over time. The goal of this work was to evaluate an emerging imaging modality, magnetic particle imaging (MPI), for intra-articular tracking of nanoparticles. MPI provides 3D visualization and depth-independent quantification of superparamagnetic iron oxide nanoparticle (SPION) tracers. Here, we developed and characterized a polymer-based magnetic nanoparticle system incorporated with SPION tracers and cartilage targeting properties. MPI was then used to longitudinally assess nanoparticle fate after intra-articular injection. Magnetic nanoparticles were injected into the joints of healthy mice, and evaluated for nanoparticle retention, biodistribution, and clearance over 6 weeks using MPI. In parallel, the fate of fluorescently tagged nanoparticles was tracked using in vivo fluorescence imaging. The study was concluded at day 42, and MPI and fluorescence imaging demonstrated different profiles in nanoparticle retention and clearance from the joint. MPI signal was persistent over the study duration, suggesting NP retention of at least 42 days, much longer than the 14 days observed based on fluorescence signal. These data suggest that the type of tracer - SPIONs or fluorophores - and modality of imaging can affect interpretation of nanoparticle fate in the joint. Given that understanding particle fate over time is paramount for attaining insights about therapeutic profiles in vivo, our data suggest MPI may yield a quantitative and robust method to non-invasively track nanoparticles following intra-articular injection on an extended timeline.
