The response to environmental and internal stimuli is one of the basic characteristics of living organisms. Inspired by this natural strategy and fast-developing nanotechnology and materials science, stimuli-responsive nanomedicine has emerged as an active and important field of nanomedicine.
This book offers a fundamental and comprehensive overview of stimuli-responsive nanomedicine and compiles and details the recent cutting-edge findings and most impressive achievements in biomedical applications, from a pharmaceutical science perspective, making it the first book of its kind in this field. By providing readers a broad and in-depth coverage of endogenous and exogenous stimuli as well as their applicable nanomedicines, this book is valuable for students, researchers, and educators in biomedical sciences or anyone interested in this burgeoning field.
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Yes, you can access Stimuli-Responsive Nanomedicine by Lin Zhu in PDF and/or ePUB format, as well as other popular books in Medicina & Teoria, pratica e riferimenti medici. We have over one million books available in our catalogue for you to explore.
Nanoscale systems have recently received tremendous attention, particularly in the field of biomedical research [1, 2]. Although drug molecules can be manipulated to improve their properties at drug discovery stage, the compatible drug delivery strategies have to be applied to facilitate the clinical applications and achieve the desirable therapeutic outcomes. In this regard, the drugs are formulated into various dosage forms or drug delivery systems. Among them, the nanoparticle-based medicine or nanomedicine is the most important one.
Therapeutic or imaging agents can be encapsulated into the inner layer or core of nanoparticles or absorbed on the surface of nanoparticles via various mechanisms. Once loaded, these molecules can be masked by the nanomaterials and drugsâ physicochemical properties as well as some other properties, such as pharmacokinetic and biodistribution profiles, are expected to be improved [3]. The most commonly used nanoparticles/nanocarriers include liposomes [4], micelles [5], dendrimers [6], lipid or polymeric nanoparticles [7, 8], emerging inorganic nanoparticles, like quantum dots, gold nanoparticles, carbon nanotubes, etc. [9â11], and macromolecule-based conjugates, such as antibody-drug conjugates (ADC) and drug-polymer conjugates (e.g., polyethylene glycol (PEG)-protein conjugates and PEG-siRNA conjugates) [12â14]. These particles typically range from 10 to 100 nm, which is considered safe and effective for most administration routes, including oral, systemic (e.g., intravenous), inhalation, ocular, and transdermal/transmucosal routes.
Thanks to the advances achieved in materials science and engineering, a broad range of nanoparticles with various sizes, morphologies, architectures, and surface properties have been developed. Moreover, the chemical or physical engineering on the surface or backbone of the nanomaterials provides additional opportunities for controlling the performance of nanomedicine. One of the most successful modification technologies is PEGylation. Due to the âstealthâ property, the PEG-modified nanoparticles are able to escape the capture by the mononuclear phagocyte system (MPS) [15], leading to the prolonged blood circulation and the enhanced permeability and retention (EPR) effect-mediated âpassiveâ tumor targeting [15, 16]. This is extremely useful for the tumor-targeted delivery of drugs and imaging agents. The nanoparticles, such as polymeric micelles, are able to extravasate into the tumors through the gaps between endothelial cells and accumulate there due to poor lymphatic drainage.
To achieve site- or cell-specific drug delivery, the nanoparticles need to be further engineered by the targeting ligands (such as monoclonal antibodies), âon-demandâ drug release/delivery moieties (such as stimuli-sensitive moieties), and the intracellular delivery moieties (such as tissue or cell-penetrating proteins or peptides).
The idea of the stimuli-responsive drug delivery comes from the fact of abnormalities in the diseased tissues or cells. For example, in the tumor microenvironment, the abnormalities include acidic pH, altered redox potential, and upregulated proteins. As shown in Fig. 1.1, these internal conditions as well as external stimuli such as hyperthermia, magnetic field, light, and ultrasound, can be employed to design a stimuli-responsive drug delivery system for on-demand and/or targeted drug delivery [17].
Generally, to construct a stimuli-responsive nanomedicine, first, we have to understand the pathological abnormalities/local stimuli or external stimuli and desirable clinical outcomes; and second, the biocompatible nanomaterials should be available for use, which may undergo conformational change, hydrolytic/enzymatic cleavage/degradation, or changes in their physico-chemical properties in response to corresponding stimuli. These physical and chemical alterations allow for the destabilization or rearrangement of the nanoparticles or âactivationâ of the blocked functions, resulting in the drug accumulation, on-demand drug release, and/or drug uptake at the disease site and/or diseased cells. A great deal of work has been dedicated to devising stimuli-sensitive polymers, biomacromolecules, and other nanomaterials. Using these âintelligentâ materials, a wide variety of stimuli-responsive nanomedicines have been developed. Here, we will overview the recent progress, highlight the important applications, and predict the future trends of stimuli-responsive nanomedicine.
1.2Typical Stimuli and Stimuli-Responsive Nanomedicines
The stimuli-responsive nanomedicine can employ the internal abnormalities in the specific tissues, cells, or even intracellular compartments, such as the abnormal pH [18], specific proteins/enzymes [19], redox potential [20], or hypoxia [21, 22]; and the physical stimuli that can be artificially applied from outside of the body, such as temperature [23], light [24], magnetic field [25], or ultrasound [26] (Fig. 1.1).
1.2.1Internal Stimuli and Stimuli-Responsive Nanomedicines
Significant alterations in the physiological condition are often the vital hallmarks for certain diseases, such as cancer and inflammatory diseases, rendering them attractive targets for designing stimuli-responsive systems. Here, we discuss the stimuli-responsive nanosystems that take advantages of the internal stimuli, including pH, enzymes, redox potential, and oxygen. The typical internal stimuli-responsive nanomedicines are summarized in Table 1.1.
Table 1.1 Examples of typical internal stimuli and stimuli-responsive nanomedicines