ABSTRACT
We compared cardiac findings in patients with multisystem inflammatory syndrome in children and Kawasaki disease in the first 6 months of the 2020 coronavirus disease pandemic to patients with Kawasaki disease during 2016-2019. We saw a high rate of coronary aneurysms in 2020, with a similar rate of coronary involvement but greater volume and incidence of cardiac dysfunction compared with previous years.
Subject(s)
COVID-19/complications , COVID-19/physiopathology , Coronary Aneurysm/physiopathology , Coronary Vessels/physiopathology , Mucocutaneous Lymph Node Syndrome/physiopathology , Systemic Inflammatory Response Syndrome/physiopathology , COVID-19/blood , Child , Child, Preschool , Coronary Aneurysm/complications , Echocardiography , Female , Humans , Immunoglobulin G , Infant , Los Angeles , Male , Mucocutaneous Lymph Node Syndrome/complications , Systemic Inflammatory Response Syndrome/blood , Systemic Inflammatory Response Syndrome/complications , Ventricular Dysfunction, Left/complications , Ventricular Dysfunction, Left/physiopathologyABSTRACT
Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer-specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light. We show that the A11 minibody strongly binds to the prostate stem cell antigen that is overexpressed on the surface of metastatic prostate cancer cells. Compared to nonconjugated gold nanoshells, our A11 minibody-conjugated gold nanoshell exhibited significant laser-induced, localized killing of prostate cancer cells in vitro. In addition, we improved upon a comprehensive heat transfer mathematical model that was previously developed by our laboratory. By relaxing some of the assumptions of our earlier model, we were able to generate more accurate predictions for this particular study. Our experimental and theoretical results demonstrate the potential of our novel minibody-conjugated gold nanoshells for metastatic prostate cancer therapy.
Subject(s)
Antigens, Neoplasm/metabolism , Gold/metabolism , Hyperthermia, Induced/methods , Immunoglobulins/metabolism , Molecular Targeted Therapy/methods , Nanoshells/chemistry , Neoplasm Proteins/metabolism , Phototherapy/methods , Cell Line, Tumor , Cell Survival/drug effects , Convection , GPI-Linked Proteins/metabolism , Humans , Infrared Rays , Low-Level Light Therapy , Male , Models, Biological , Models, Theoretical , Prostatic Neoplasms/therapy , Surface Plasmon ResonanceABSTRACT
Targeted killing of cancer cells by engineered nanoparticles holds great promise for noninvasive photothermal therapy applications. We present the design and generation of a novel class of gold nanoshells with cores composed of self-assembled block copolypeptide vesicles with photothermal properties. Specifically, poly(L-lysine)60- block-poly(L-leucine)20 (K60L20) block copolypeptide vesicles coated with a thin layer of gold demonstrate enhanced absorption of light due to surface plasmon resonance (SPR) in the near-infrared range. We show that the polypeptide-based K60L20 gold nanoshells have low toxicity in the absence of laser exposure, significant heat generation upon exposure to near-infrared light, and, as a result, localized cytotoxicity within the region of laser irradiation in vitro. To gain a better understanding of our gold nanoshells in the context of photothermal therapy, we developed a comprehensive mathematical model for heat transfer and experimentally validated this model by predicting the temperature as a function of time and position in our experimental setup. This model can be used to predict which parameters of our gold nanoshells can be manipulated to improve heat generation for tumor destruction. To our knowledge, our results represent the first ever use of block copolypeptide vesicles as the core material of gold nanoshells.
