Engineering All-in-one Protein-based Nanoparticles for Targeted Cancer Therapies


Book Description

Actualmente, las terapias convencionales contra el cáncer están lejos de ser ideales en cuanto a eficacia. Los fármacos actuales, formados por pequeños compuestos químicos se distribuyen indistintamente por todo el organismo, generando elevada toxicidad sistémica y dando lugar a efectos secundarios en tejidos sanos. En este contexto, la nanomedicina es una disciplina emergente que ofrece alternativas prometedoras para el desarrollo de terapias innovadoras y mejoradas contra el cáncer. Siendo materiales especialmente versátiles, las proteínas recombinantes están ganando mucho interés en el área de la biomedicina, con más de 400 fármacos recombinantes aprobados por agencias médicas. Las nanopartículas modulares y multifuncionales con naturaleza proteica son grandes candidatos para la entrega de fármacos ya que presentan gran estabilidad, biocompatibilidad y biodegradabilidad en el torrente sanguíneo. A la hora de diseñar sistemas para la administración de fármacos, el tamaño es una de las características más relevantes. Partículas dentro de la nanoescala (alrededor de los ̃8 - 100 nm) poseen una mayor estabilidad ya que pueden escapar de la filtración renal y por tanto tienen un mayor tiempo de circulación y mejor biodistribución (comparado con los compuestos químicos de menor tamaño). Por eso en nuestro grupo se ha desarrollado un principio nanoarquitectónico para el desarrollo de ensamblajes proteicos comprendidos en la nanoescala. Este principio se fundamenta en el uso de péptidos terminales catiónicos, para la oligomerización de monómeros en nanopartículas auto-ensambladas. Estas nanoestructuras proteicas modulares pueden ser empleadas como vehículos dirigidos a células si el péptido catiónico situado en el extremo N-terminal es además un ligando especifico de tumor. Sin embargo, la conjugación química de estos vehículos a un fármaco convencional conlleva riesgos debido a posibles liberaciones del mismo y posteriores efectos secundarios. Por todo ello, el principal objetivo de esta tesis ha sido explorar la aplicabilidad de este principio para el desarrollo de nanomedicinas proteicas multifuncionales y libres de vehículos adicionales. Este propósito se ha llevado a cabo mediante el diseño racional de novo de proteínas intrínsecamente citotóxicas como entidades terapéuticas para desarrollar fármacos antitumorales proteicos dirigidos a tumor. A partir de ahora, a raíz de los prometedores resultados discutidos en esta tesis, consideramos que es necesario seguir estudiando en profundidad la potencial aplicación de esta plataforma proteica multifuncional para el tratamiento de muchas otras enfermedades.




Cancer Nanotheranostics


Book Description

Nanotechnology is an interdisciplinary research field that integrates chemistry, engineering, biology, and medicine. Nanomaterials offer tremendous opportunity as well as challenges for researchers. Of course, cancer is one of the world's most common health problems, responsible for many deaths. Exploring efficient anticancer drugs could revolutionize treatment options and help manage cancer mortality. Nanomedicine plays a significant role in developing alternative and more effective treatment strategies for cancer theranostics. This book mainly focuses on the emerging trends using nanomaterials and nanocomposites as alternative anticancer material’s. The book is divided into three main topic areas: how to overcome existing traditional approaches to combat cancer, applying multiple mechanisms to target the cancer cells, and how nanomaterials can be used as effective carriers. The contents highlight recent advances in interdisciplinary research on processing, morphology, structure, and properties of nanostructured materials and their applications to combat cancer.Cancer Nanotheranostics is comprehensive in that it discusses all aspects of cancer nanotechnology. Because of the vast amount of information, it was decided to split this material into two volumes. In the first volume of Cancer Nanotheranostics, we discuss the role of different nanomaterials for cancer therapy, including lipid-based nanomaterials, protein and peptide-based nanomaterials, polymer-based nanomaterials, metal-organic nanomaterials, porphyrin-based nanomaterials, metal-based nanomaterials, silica-based nanomaterials, exosome-based nanomaterials and nano-antibodies. In the second volume, we discuss the nano-based diagnosis of cancer, nano-oncology for clinical applications, nano-immunotherapy, nano-based photothermal cancer therapy, nano-erythrosomes for cancer drug delivery, regulatory perspectives of nanomaterials, limitations of cancer nanotheranostics, the safety of nano-biomaterials for cancer nanotheranostics, multifunctional nanomaterials for targeting cancer nanotheranostics, and the role of artificial intelligence in cancer nanotheranostics.




Nanoparticle-Based Drug Delivery in Cancer Treatment


Book Description

The careful choice of nanoparticles as targets and in drug delivery routes enhances therapeutic efficacy in cancer. Nanoparticle-Based Drug Delivery in Cancer Treatment discusses nanotechnological developments of interfering RNA-based nanoparticles, delivery vehicles, and validated therapeutic RNAi–molecular target interactions and explains the results of clinical and preclinical trials. The book also gives strategies for universal methods of constructing hybrid organic–inorganic nanomaterials that can be widely applied in the biomedical field. Key Features: Reviews recent advances of nanoparticle-mediated siRNA delivery systems and their application in clinical trials for cancer therapy Focuses on material platforms that establish NPs and both localized and controlled gene silencing Emphasizes the most promising systems for clinical application Surveys progress in nanoparticle-based nanomedicine in cancer treatment Describes the most advanced of the nonviral nanocarriers for delivery of oligonucleotides to malignant blood cancer cells This book is a valuable resource for researchers, professors, and students researching drug delivery, gene carriers, cancer therapy, nanotechnology, and nanomaterials.




Nanotechnology-Based Precision Tools for the Detection and Treatment of Cancer


Book Description

This book discusses emerging nanotechnology-based tools that have the potential to dramatically impact cancer research, diagnostics, and treatment. Cancer is a complex, devastating, and debilitating disease and, although much progress has been made, novel, more effective diagnostic and treatment options are still needed, especially for advanced cancers. The ultimate goal is to detect cancer early and non-invasively and to provide efficacious and targeted precision treatments that cause fewer harmful side effects. This book explains how nanotechnology can exploit the size-, shape-, and composition-dependent properties of nanomaterials to provide novel tools for precision cancer medicine. It will be of interest to researchers and professionals working in the fields of chemistry, biology, materials science and engineering, and medicine who want to learn more about this fascinating and fast-paced area of research.




Viral Nanoparticles


Book Description

This book overviews the applications of viral nanoparticles (VNPs) in areas ranging from materials science to biomedicine. It summarizes the many different VNP building blocks and describes chemistries that allow one to attach, entrap, or display functionalities on VNPs. The book outlines the strategies for the construction of 1-, 2-, and 3-D arrays, highlights the achievements in utilizing VNPs as tools for novel biosensors and nanoelectronic devices, and describes efforts in designing VNPs for biomedical applications, including their use as gene delivery vectors, novel vaccines, imaging modalities, and applications in targeted therapeutics.




Multifunctional Nanoparticles for Drug Delivery Applications


Book Description

This book clearly demonstrates the progression of nanoparticle therapeutics from basic research to applications. This book, unlike others covering nanoparticles used in medical applications, presents the medical challenges that can be reduced or even overcome by recent advances in nanoscale drug delivery. Each chapter highlights recent progress in the design and engineering of select multifunctional nanoparticles with topics covering targeting, imaging, delivery, diagnostics, and therapy.




Emerging Trends in Immunomodulatory Nanomaterials Toward Cancer Therapy


Book Description

Recently, immunomodulatory nanomaterials have gained immense attention due to their involvement in the modulation of the body’s immune response to cancer therapy. This book highlights various immunomodulatory nanomaterials (including organic, polymer, inorganic, liposomes, viral, and protein nanoparticles) and their role in cancer therapy. Additionally, the mechanism of immunomodulation is reviewed in detail. Finally, the challenges of these therapies and their future outlook are discussed. We believe this book will be helpful to a broad community including students, researchers, educators, and industrialists.




Bio-Nanomedicine for Cancer Therapy


Book Description

The book covers the latest developments in biologically-inspired and derived nanomedicine for cancer therapy. The purpose of the book is to illustrate the significance of naturally-mimicking systems for enhancing the dose delivered to the tumor, to improve stability, and prolong the circulation time. Moreover, readers are presented with advanced materials such as adjuvants for immunostimulation in cancer vaccines. The book also provides a comprehensive overview of the current status of academic research. This is an ideal book for students, researchers, and professors working in nanotechnology, cancer, targeted drug delivery, controlled drug release, materials science, and biomaterials as well as companies developing cancer immunotherapy.




Protein Engineering for Cancer Therapy


Book Description

The immunosuppressive effects of CD4+CD25+ regulatory T cells (Tregs) interfere with anti-tumor immune responses in cancer patients. In the first part of this work, we present a novel class of engineered Interleukin-2 (IL-2) analogues that antagonize the IL-2 receptor, for inhibiting Treg suppression. These antagonists are engineered for high affinity to the IL-2 receptor a subunit and low affinity to either the [beta] or [gamma] subunit, resulting in a signaling-deficient IL-2 analogue that sequesters the IL-2 receptor a subunit from wild type IL-2. Using this design, human and mouse IL-2 antagonists were generated with inhibition constants ranging from 200 pM to 5 nM in vitro. Genetic fusions with IgG2a Fc enhanced serum half-life up to 30 hours. In order to study the effects of IL-2 antagonism, Fc fragments with disrupted effector functions were used. Fc-antagonist fusions bound to but could not deplete peripheral Tregs. They downregulated CD25 on Tregs, but could not perturb Treg function in a syngenic tumor model, presumably due to the high sensitivity of the IL-2 receptor and a high threshold for antagonism in vivo. In the second part of this work, we present a novel multi-agent protein-based system for targeted siRNA delivery that provides potential advantages over other nanoparticle- and proteinbased delivery vehicles. In the first agent, the double stranded RNA binding domain (dsRBD) of human protein kinase R is used as an siRNA carrier, in fusion proteins that target epidermal growth factor receptor (EGFR). Targeted dsRBD proteins deliver large amounts of siRNA to endosomal compartments in an EGFR expressing cell line, but efficient gene silencing is limited by endosomal escape. The use of a second agent that contains the cholesterol dependent cytolysin, perfringolysin 0, enhances endosomal escape of siRNA. Targeted delivery of perfringolysin 0 induces gene silencing in a dose-dependent and EGFR-dependent manner. However, cytotoxicity of the cytolysin creates a narrow therapeutic window. Multiepitopic EGFR binders that induce EGFR clustering are explored as tools for enhancing gene silencing efficiency. Interestingly, they not only enhance gene silencing potency but also protect against toxicity from EGFR-targeted cytolysins, thus significantly widening the therapeutic window of this method.




Engineered Nanomaterials for Innovative Therapies and Biomedicine


Book Description

Research on biomedical applications of nanomaterials has exhibited the rapidly evolving field of biomedical sciences by showing how effective they are in treatment. These particles hold considerable potential for biomedical applications. Work is ongoing, and the results suggest a possibility for a sustainable future for nanomaterials in both therapeutic and biomedical fields. This book highlights current and emerging applications, taking global research findings into consideration. We believe the focus on the identification and role of nanomaterial applications in therapeutic and biomedical sciences can lead to novel solutions in the fields. The chapters of this book are disseminated in a manner that can be readily adopted as sources for new and further study. The editors integrate advanced texts in their research that help graduate students, researchers and professors. Additionally, we believe that international readers will be able to make use of this book for reference purposes.