The World Scientific Encyclopedia of Nanomedicine and Bioengineering II

The following sections are included:

• Contents
• Preface
• About the Editor

Positron Emission Tomography (PET) is one of the most sensitive imaging techniques and has been widely used in tumor diagnosis. It can provide a noninvasive and regional estimation of a specific organ with its biochemical processes by introducing a radioactive isotope labeled molecule. Radiolabeled nanoparticles, which have unique characteristics such as large surface area, multifunctionality and long circulation, show great potential in molecular imaging. In this article, we describe the advances in the development of nanoparticle-based tumor PET imaging. Besides the types of radiolabeled nanoparticles (iron-oxide nanoparticles, quantum dots, upconversion nanoparticles (UCNPs), mesoporous silica nanoparticles (MSNs)), the radionuclides, targeting strategies and multimodality imaging are also mentioned.

Nanoparticles such as gold and silver nanoparticles are used widely in biomedical researches and clinical diagnosis. This chapter mainly introduces the nanoparticles used in biomedical applications as the enhance substrate for Raman spectroscopy technology. Nanoparticles with different shapes, sizes, structures, arrangements, coatings and labels, made the Raman spectroscopy easy to detect precancerous and early cancerous changes, which have great significance in the diagnosis of cancer. Raman spectroscopy with nanoparticles has the advantages of being fast, sensitive and label-free in cancer diagnosis and biological applications.

Superparamagnetic iron oxide nanoparticles (SIONPs) have received great attention when they are applied as contrast agents for magnetic resonance imaging (MRI). Recent developments and biological applications of polymeric nanomaterials contained with SIONPs are summarized. This chapter discusses the synthesis of magnetic iron oxide polymeric nanoparticles and their MRI applications, especially in molecular imaging of organs and tumors. Classification, design, preparation and MRI biomedical application of iron oxide-based superparamagnetic polymeric nanomaterials are discussed. SIONP modified with nature polymers (dextran, chitosan, liposome), synthetic polymers, polymers with peptide, protein, target polymers and drug delivery system of polymers all can be used in MRI.

Gold nanoparticles (AuNPs) hold great promise for the clinical applications. They have a series of advantages including bio-inert nature, well-controlled morphologies, easy surface modification and unique optical properties, and have been proven to be an excellent scaffold for diverse biomedical applications including diagnosis, imaging and therapies. In this chapter, we first introduce four typical AuNPs that can be well developed for biomedical usage, and discuss their optical properties and surface modifications. Then, we address the important application of AuNPs as a contrast agent or fluorescent probe for the diagnosis/imaging of cancers in vitro and in vivo, and further discuss their use for photothermal therapy and as a vehicle for gene and drug delivery.

Graphene quantum dots (GQDs), single- or few-layer graphene (GO) with a tiny size of less than 100 nm, emerged as a new type of carbon quantum dots. Due to quantum confinement and edge effects, GQDs with extraordinary properties have attracted extensive attention of scientists and have been explored for their application in the fields of chemistry, physics, materials, biology and other interdisciplinary sciences. In this paper, we mainly focus on the biomedical application of GQDs, such as in vitro and in vivo labeling in cell, tissues and organisms for disease diagnosis, drug delivery with selective tumor targeting and biological cancer therapeutics.

Applications of magnetic particles in cancer therapy include delivering drugs to tumors, hyperthermia therapy under alternating magnetic field (AMF), cancer photothermal therapy (PTT) and promoting apoptosis-signaling pathways by magnetic switching. In recent years, a novel method to kill cancer cells using magnetic field-mediated mechanical stimulation has attracted extensive attention. In this technique, magnetic particles vigorously vibrate, oscillate or rotate under low-frequency AMF and transfer the magnetomechanical force to cancer cells, damaging them. Although a force of hundreds of piconewtons (pN) is required to effectively destroy cancer cells, a force of only tens of PN can induce cell apoptosis, because the permeability of the cell membrane may be increased following exposure to a small force. In this chapter, the advantages of this novel physical cancer therapy based on mechanical force are discussed. The influence of the morphology of the magnetic particles on their ability to kill cells and the operational details of this method are also presented. Finally, the development trends and biological safety of this technique are described.

Tumor extracellular acidity-sensitive polymeric nanocarriers provide a new strategy to enhance the therapeutics efficacy for cancer therapy. Compared to conventional surface ligand decoration approaches, the pH_e-targeting strategy is considered to have more potential due to the common occurrence of acidic microenvironment in solid tumors. This chapter focuses on the design and applications of pH_e-sensitive polymeric nanocarriers for drug and siRNA delivery for tumors. The development of these nanocarriers described here demonstrates great improvement of therapeutic effects in cancer treatment.

For the past few decades, there has been a considerable research interest in the area of nanoparticulate systems using polysaccharides derivatives as carriers for anticancer agents to improve the pharmacokinetic and pharmacodynamic properties of such agents. Indeed, natural polysaccharides are being widely explored for the development of new nanosystems for clinical application due to their favorable features such as biocompatibility, biodegradability and low immunogenicity as well as the targeting ability and biological activities, which are rarely realized by their synthetic counterparts. Numerous investigations have shown that polysaccharidesbased nanoparticles (NPs) have the potential to enhance the therapeutic efficacy of cytotoxic agents through increasing their solubility, stability and circulation time while protecting them from degradation or premature metabolism and elimination by phagocytes. Moreover, they can improve the tissue and cell distribution profiles of anticancer agents due to enhanced permeability and retention effect, controlled release characteristics or by active targeting, and thus increase their antitumor efficacy and reduce systemic side effects. Polysaccharide-based NPs injections and oral preparations have been widely used to deliver anticancer drugs, photodynamic therapeutic agents and so on. This chapter will focus on the application of various polysaccharides-based NPs for tumor-targeted delivery.

The lack of safe and effective carrier systems are preventing the use of DNA and siRNA as therapeutic drugs. To overcome this hurdle, extensive research has been performed on synthetic delivery systems because they are easily produced and formulated, and exhibit great capacity to condense nucleic acids. However, the low transfection efficiency and high chemical toxicity inhabit the clinical application of synthesized carriers, until now, thousands of nonviral nucleic acids showed their own advantages to solve the problem of nucleic acid delivery theoretically, whereas the nonviral vectors were still investigated as the experimental reagents. It indicates that some key biological barriers have not been overcome. On the other hand, a large study gives the hope to completely solve the problem of nucleic acid delivery, for example the enhanced design of lipopolyplexes based on polyplexes (which were formed by cationic polymers and nucleic acids) and lipoplexes (which were formed by cationic liposomes and nucleic acids) have improved the transfection efficiency of nucleic acids and dropped the cytotoxicity of delivery system in vitro and in vivo, In the present text, we will mainly focus on lipoplexes and polyplexes, and lipopolyplexes, and discuss and analyze the rational design of nucleic acid delivery for therapeutic application.

Liposome, which was used successfully in clinics as the first drug-loading nanoparticle is now becoming the popular nanoparticle drug delivery system in pharmaceutics. In 1960s, Bangham and his colleagues first described the bilayer structure of phospholipids as the lipids were dispersed and swollen in aqueous solution. Then in a few years, studies established lipid-based bilayer vesicles could be employed as drug delivery systems and have impact on the in vivo distribution of entrapped drug. But the path is long and winding from the concept of clinical application of liposomes to their acceptance and recognized position in the mainstream of drug delivery systems. For the 1st generation (classic) liposomes, which always accompanied a number of problems, such as the difficulty in retaining some active agent in the liposome interior, the drug release affected by serum proteins, the rapid clearance after system administration and the failure of intracellular delivery of drugs.

With the recognition of these problems, came research on designing liposomes to achieve optimized properties. Figures 1 and 2 show different liposome structures developed in the study of loading small molecular therapeutic drugs (SMTDs) into liposomes. Many improvements and efforts have been made in the past 40 plus years to achieve the clinical success of liposome products, especially work done with the SMTDs, which we will discuss in detail as follows.

The following section is included:

• Index