Hard Template-Directed Synthesis

Abstract

Silica is presently widely used as a template for the development of various nanostructures due to its characteristic high surface area, thermal and chemical resistance, the presence of reactive silanol groups (Si–OH), and nanopores. Nontraditional nanostructures consisting of noble metals are often fabricated by depositing thin layers of metals (or their precursors) on some silica beads existing templates. A straightforward sol-gel method can be utilized for the preparation of noble metal nanoparticles and their composites via in situ-doped silica aerogels. The metal dispersion and size distribution obtained by this approach depends on the kind of metal, the reaction conditions, and the metal loading. Another approach consisted of making use of the pore channels of hexagonal mesoporous silica, as matrixes for controlling the nanoparticles size. It was demonstrated that noble metal nanoparticles could be coated with a silica shell via the reaction of citrate-stabilized gold nanoparticles and alkylaminotrimethoxysilane, followed by polymerization after the addition of a sodium silicate solution. The spherical silica nanoparticles were used as the templates of interior cores of metal nanoshells and as the templates for the deposition of the external noble metal shell layer by layer. A controlled growth of silver nanoparticles on TiO₂ templates is expected in tuning the optical response of the silver–TiO₂ hybrids. The growth model can explain the phenomenon of silver nanoplates lying on the small silver nanoparticles. A simple and reproducible method for the activation of monodispersed silver nanoparticles was insertion of the concentrated NaCl, NaBr, and NaI solution into the silver nanoparticle dispersion. It was also demonstrated the entrapment of thiol-coated gold particles, and believe that the technique is straightforwardly applicable also for other hydrophobically coated nanoparticles. The presence of a substrate influences the resultant frequency and bandwidth of the surface plasmon resonance and more generally its multipole distribution. By combining two different materials or different particle shapes of the same material within the same single nanostructure, new properties of the coupled system can be obtained. An interesting approach to introduce theranostic functionalities into a nanosystem is to covalently attach a metal-porphyrin chelate to mesoporous silica nanoparticles (MSNs) which are readily taken up by cells. Bioconjugates based on MSNs are used in a wide array of applications, including chemical catalysis, drug delivery, controlled release of therapeutics, and cell labeling and killing. UV-photoexcited TiO₂ nanoparticles and their conjugates in aqueous solution form various reactive oxygen species, mainly highly reactive hydroxyl (OH), peroxy (HO₂) radicals, and singlet oxygen, highly reactive hydroxyl radicals, electrons and superoxide ions able to deactivate of bacteria, algae, viruses and kill cancer cells.

Glossary

Antibody (Ab )

is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to identify and neutralize pathogens such as bacteria and viruses . The antibody recognizes a unique molecule of the harmful agent, called an antigen, via the Fab’s variable region. Each tip of the “Y” of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (similarly analogous to a key) on an antigen, allowing these two structures to bind together with precision. Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize its target directly (e.g., by blocking a part of a microbe that is essential for its invasion and survival). Depending on the antigen , the binding may impede the biological process causing the disease or may activate macrophages to destroy the foreign substance. The ability of an antibody to communicate with the other components of the immune system is mediated via its Fc region (located at the base of the “Y”), which contains a conserved glycosylation site involved in these interactions. The production of antibodies is the main function of the humoral immune system.

Antigen

is a molecule capable of inducing an immune response on the part of the host organism, though sometimes antigens can be part of the host itself. Each antibody is specifically produced by the immune system to match an antigen after cells in the immune system come into contact with it; this allows a precise identification of the antigen and the initiation of a tailored response. The antibody is said to “match” the antigen in the sense that it can bind to it thanks to adaptations performed to a region of the antibody; because of this, many different antibodies can be produced, with specificity to bind many different antigens while sharing the same basic structure.

Apoptosis

is a process of programmed cell death that occurs in multicellular organisms . Biochemical events lead to characteristic cell changes (morphology) and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, chromosomal DNA fragmentation, and global mRNA decay. Between 50 and 70 billion cells die each day due to apoptosis in the average human adult. Apoptosis is a highly regulated and controlled process that confers advantages during an organism’s lifecycle. Apoptosis produces cell fragments called apoptotic bodies that phagocytic cells are able to engulf and quickly remove before the contents of the cell can spill out onto surrounding cells and cause damage to the neighboring cells.

Astrocytes

are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical support of endothelial cells that form the blood–brain barrier , provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a role in the repair and scarring process of the brain and spinal cord following traumatic injuries.

Cancer cells

are cells that divide relentlessly, forming solid tumors or flooding the blood with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, and these daughter cells are used to build new tissue, or to replace cells that have died as a result of aging or damage. Healthy cells stop dividing when there is no longer a need for more daughter cells, but cancer cells continue to produce copies. They are also able to spread from one part of the body to another in a process known as metastasis.

Carcinoembryonic antigen (CEA )

describe a set of highly related glycoproteins involved in cell adhesion. CEA is usually present only at very low levels in the blood of healthy adults. However, the serum levels are raised in some types of cancer, which means that it can be used as a tumor marker in clinical tests . Serum levels can also be elevated in heavy smokers. CEA are glycosyl phosphatidyl inositol (GPI) cell-surface-anchored glycoproteins whose specialized sialofucosylated glycoforms serve as functional colon carcinoma L-selectin and E-selectin ligands, which may be critical to the metastatic dissemination of colon carcinoma cells.

Central nervous system (CNS )

is the part of the nervous system consisting of the brain and spinal cord. The central nervous system is so named because it integrates information it receives from and coordinates and influences the activity of all parts of the bodies of bilaterally symmetric animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish—and it contains the majority of the nervous system.

Chemotherapy

as a treatment of cancer often relies on the ability of cytotoxic agents to kill or damage cells which are reproducing; this preferentially targets rapidly dividing cancer cells. This cancer treatment uses one or more anticancer drugs (chemotherapeutic agents) as part of a standardized chemotherapy regimen. It may be given with a curative intent (which almost always involves combinations of drugs), or it may aim to prolong life or to reduce symptoms (palliative chemotherapy). Chemotherapy is one of the major categories of medical oncology (the medical discipline specifically devoted to pharmacotherapy for cancer).

Cytotoxicity

is the quality of being toxic to cells. Examples of toxic agents are an immune cell or some types of venom, e.g., from the puff adder (Bitis arietans) or brown recluse spider (Loxosceles reclusa).

Dopamine (3,4-dihydroxyphenethylamine)

is an organic chemical of the catecholamine and phenethylamine families that plays several important roles in the brain and body. It is an amine synthesized by removing a carboxyl group from a molecule of its precursor chemical l-DOPA, which is synthesized in the brain and kidneys. Dopamine is also synthesized in plants and most multicellular animals. In the brain, dopamine functions as a neurotransmitter—a chemical released by neurons (nerve cells) to send signals to other nerve cells. The brain includes several distinct dopamine pathways, one of which plays a major role in reward-motivated behavior. Most types of reward increase the level of dopamine in the brain, and many addictive drugs increase dopamine neuronal activity. Other brain dopamine pathways are involved in motor control and in controlling the release of various hormones. These pathways and cell groups form a dopamine system which is neuromodulatory.

Doxorubicin

is a medication used in cancer chemotherapy. It is commonly used in the treatment of a wide range of cancers, including hematological malignancies (blood cancers, like leukemia and lymphoma), many types of carcinoma (solid tumors), and soft tissue sarcomas . It is often used in combination chemotherapy as a component of various chemotherapy regimens.

Imaging agents

are chemicals designed to allow clinicians to improve the imaging of specific organs, tissues, diseases, and physiological functions.

Interleukin (IL ),

any of a group of naturally occurring proteins that mediate communication between cells. Interleukins regulate cell growth, differentiation, and motility. They are particularly important in stimulating immune responses, such as inflammation . Interleukins are a group of cytokines (secreted proteins and signal molecules) that were first seen to be expressed by white blood cells (leukocytes). The interleukin-13 receptor (IL13R) is a type I cytokine receptor, binding Interleukin-13. It consists of two subunits, encoded by IL13RA1 and IL4R, respectively. These two genes encode the proteins IL-13Rα1 and IL-4Rα. These form a dimer with IL-13 binding to the IL-13Rα1 chain, and IL-4Rα stabilizes this interaction. This IL-13 receptor can also instigate IL-4 signaling. In both cases, this occurs via activation of the Janus kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) pathway, resulting in phosphorylation of STAT6. Phosphorylated STAT6 dimerises and acts as a transcription factor activating many genes.

Monoclonal antibodies (mAb or moAb)

are antibodies that are made by identical immune cells that are all clones of a unique parent cell. Monoclonal antibodies can have monovalent affinity, in that they bind to the same epitope (the part of an antigen that is recognized by the antibody). In contrast, polyclonal antibodies bind to multiple epitopes and are usually made by several different plasma cell (antibody secreting immune cell) lineages. Bispecific monoclonal antibodies can also be engineered, by increasing the therapeutic targets of one single monoclonal antibody to two epitopes. Given almost any substance, it is possible to produce monoclonal antibodies that specifically bind to that substance; they can then serve to detect or purify that substance. This has become an important tool in biochemistry, molecular biology, and medicine. Monoclonal antibodies (mAbs) have become a successful therapeutic drug class due to their specificity, efficacy, and the low level of adverse effects they induce. They are single-targeting molecules meaning that all antibodies in a drug product are identical and therefore bind specifically to only one binding site on one target. Such single-targeting molecules offer specificity but not diversity, which may help explain why a recombinant mAb drug is less likely to completely neutralize or eliminate targets involved in disease, and consequently why mAbs may provide limited clinical benefit.

Photodynamic therapy (PDT )

is a clinically approved and minimally invasive therapy that uses a nontoxic light-sensitive compound (photosynthesizer ) that is readily absorbed by abnormal cells. When exposed to a specific wavelength of light, the photosynthesizer is activated to produce changes in endothelial cell integrity that ultimately produce vascular disruption .

Prostate-specific antigen (PSA ),

also known as gamma-seminoprotein or kallikrein-3 (KLK3), is a glycoprotein enzyme encoded in humans by the KLK3 gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland. PSA is present in small quantities in the serum of men with healthy prostates, but is often elevated in the presence of prostate cancer or other prostate disorders.

Therapeutic agent

is a structure of natural or synthetic origin used for its specific action against disease, usually against infection. A therapeutic effect is a consequence of a medical treatment of any kind, the results of which are judged to be desirable and beneficial.

Therapy agents

are used to modify the relationship between tumor and host, altering the host’s biological response to tumor cells, with a resultant therapeutic effect. Most therapy agents are designed to activate the patient’s immune system and induce it to attack cancer cells. Common biological agents that have been approved for use in treating specific types of cancer are interferons , monoclonal antibodies, interleukins, tumor vaccines , etc.