Zohaib HUSSAINApplication of Biological Assemblies in

NanoBiotechnology

What is Biological Assemblies ?• The biological assembly (also sometimes referred to as the

biological unit) is the macromolecular assembly that has either

been shown to be or is believed to be the functional form of the

molecule. For example, the functional form of hemoglobin has four

chains.

• Depending on the particular crystal structure, symmetry operations

consisting of rotations, translations or their combinations may need

to be performed in order to obtain the complete biological

assembly.

Preparations

Thus, a biological assembly may be built from:

1. One copy of the asymmetric unit

2. Multiple copies of the asymmetric unit

3. A portion of the asymmetric unit

Hemoglobin is used again to demonstrate each of these cases:

The Use of Drug Nanocrystals

for Improved Application • To improve the effect of pharmaceutical products is to

form nanocrystals of the desired drug.

• This is in contrast to the unordered powder or solidified

powder as commonly used.

• The size of the nanocrystals is in nano-scale and is in the

order of 200-500 nm.

• The nanocrystals are then administered as a suspension

in aqueous solution

Advantages over simple drug formulations

1. Much better solubility for

hydrophobic drugs which are not

water-soluble.

2. It improves the bioavailability of the

drug for absorption in the digestive

track.

3. it improves the stability of the drug

to biological degradation in the

body, as well as chemical and

physical degradation which is

reflected by a longer shelf life.

• Examples

One of the early nanocrystal drugs

approved by the FDA is the

immunosuppressant Rapamuneo of

Wyeth Pharmaceuticals. Significantly

improved the availability and

pharmacokinetics of the drug.

• Current research

Current attempts are being made in the

nano formulation of large peptide drugs

such as insulin and other hormones for

oral administration.

The Use of Nano-Containers for Drug

Delivery

The use of heterologous Nano-

containers for drug delivery e.g lipid

vesicle self-assembly, one of the

earliest applications of liposomes is

the delivery of drugs to specific organs

The liposomes have many advantages

1. Relative stability

2. Ability to retain biological molecules

with a low rate of leakage.

3. Composed of natural biomolecules

and thus are recognized as "self"

material by the human body(

biocompatibility ).

4. Chemical functionality allows their

decoration with various biological

and chemical molecules for specific

targeting of the vesicles by high

affinity to specific ligands or

receptors.

5. Such high affinity is crucial for the

delivery of highly toxic drugs such as

chemotherapy agents.

6. The specific targeting reduce side

effects due to minimal exposure of

the healthy tissue to the drug.

7. The encapsulation of the drug

within the nano-container also affects

the absorption, distribution, and

metabolism of the drug

Other Applications The liposomes used for the delivery of other materials such as DNA.

1. Applications of liposome technology for gene therapy, as normal genes can

be transferred to cells carrying mutated, non-functional ones. This may be

useful for various genetic diseases such as cystic fibrosis in which the

newborn carries a mutated gene that does not allow a normal function. And

also for tumor gene cure

2. As an alternative to the current application of viral vectors to deliver the

genes of interest. The use of the viral vectors is problematic due to various

side effects resulting from the viral integration into the patient genome. Thus,

a bio-logically inert delivery system may offer various advantages.

The Use of S-Layers for Nanolithography

• Uwe Sleytr and co-workers to demonstrate that it is possible to

recrystallize S-layer subunits on various substrates which are

suitable for nanofabrication, such as silicon or silicon oxide wafers

and also on lipid membranes or at the air—water interface.

• These marvelous self-assembled nano-structures were demon-strated

to be very useful for lithographic applications.

• Purified S-layer building blocks spontaneously reassemble into

well-ordered two-dimensional crystals under in vitro conditions.

• S-layers have also been used as binding templates for well-organized

arrangements of nanoparticles, such as semiconductors and metallic

dots, and also for biomolecules such as enzymes and antibodies.

Procedure

• This type of assembly and molecular interaction allowed the

application of the crystal-line arrays as patterning media for Nano-

scale lithography

• It was demonstrated that it is possible to pattern S-layers using

ultraviolet radiation

• S-layers that were ordered on a silicon wafer are brought into direct

contact with a photo mask and exposed to ultraviolet irradiation.

Such lithographic patterning of the layers, together with specific

patterning of inorganic molecules and biomolecules could allow the

fabrication of a lab-on-a-chip. .

Figure : schematic drawing of partitioning of s-layer on the silicon

wafer by using a Duv radiation and laser

The Use of Peptide Templates

for Biomineralization

Although most of the building blocks in biology are based

on organic, carbon-dominated building blocks such as

proteins, nucleic acids, poly-saccharides, and

phospholipids, the role of inorganic materials could not

neglected

Multifunctional β-sheet peptide template for calcium

carbonate mineralization. The template self-supplies the

mineral source, a carbonate ion, by hydrolysis of urea, and

regulates the crystal phase and morphology of the obtained

calcium carbonate

The Utilization of Biomineralization

in Nanotechnology

• There is a great interest in the utilization of biomineralization in Nano-technology.

• The ability to form complex inorganic structures. such as artificial bones and teeth, using biological templates which will direct inorganic organization may change the face of modem medicine

• Extraction and purification of all the proteins involved is quite a technical challenge, therefore many in vitro approaches employ self-assembling building blocks endowed with templating activity.

• Knowledge of the mechanisms of biomineralization can lead to the nanofabrication of artificial building blocks which emulate the original biotemplating behavior.

• One example of such an approach is the use of a peptide

fragment, silaffin-1 internal repeats protein, which mediates

silica organization.

• The peptide fragment, which comprises the amino acid

sequence of one repeat unit, can direct and affect the

morphology of silica organization at near neutral pH

• Designer self-assembling peptides can be targeted for silica

deposition through the introduction of positively charged

residues which attract negatively charged silica precursors.

Such examples include the 13-hairpin or a-helical

• Peptides Silicate in filaments are able to template not only

silica, but also non-biogonic oxides such as titanium dioxide

and gallium oxide at ambient temperatures and near neutral pH.

Refrences

1. http://www.rsc.org/suppdata/cc/c3/c3cc44947e/c3cc449

47e.pdf

2. Samori, Bruno. "Plenty of Room for Biology at the

Bottom. An Introduction to Bionanotechnology. By

Ehud Gazit." (2008): 236-237.

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