Nanobiotechnology

Nanobiotechnology (also called nanomedicine, bionanotechnology, or nanobiology) is an emerging field at the intersection of biology and nanomaterials science.

At nanoComposix, we design and fabricate nanomaterials that perform specific functions inside biological systems. For more information about nanomedicine capabilities at nanoComposix, visit our Nanomedicine CDMO Services page.

Our nanoparticles can be engineered to:

Be tracked inside the body
Deliver a compound at a controlled rate
Target a specific location
Remotely destroy cells after reaching a target

We can build in functionalities such as:

Fluorescence
Magnetic properties
Light scattering
Drug delivery

In many cases, biomolecules such as antibodies, oligonucleotides, or peptides are attached to the particle surface. These molecules help direct the particle to a specific target.

To extend circulation time, nanoparticles can be protected with a stealth coating that allows the nanoparticle to avoid the body’s scavenging mechanisms.

Targeting

One key advantage of nanoparticles is their ability to target specific locations in the body.

Once nanoparticles reach their destination, they can:

Act as imaging reporters
Release a therapeutic compound
Be remotely heated to damage nearby biological structures

Targeting is usually achieved by modifying the nanoparticle surface with chemical or biological compounds.

Passive Targeting

In some cases, targeting is passive. Accumulation in areas such as tumors occurs mainly due to nanoparticle size.

For example, Nanospectra Biosciences uses gold nanoshells to passively accumulate at tumor sites through a process called Enhanced Permeability and Retention (EPR). Tumors have increased vasculature, which allows circulating nanoparticles to deposit directly into the tumor.

Active Targeting

In active targeting, biological recognition molecules are attached to the nanoparticle surface. The most common targeting elements are antibodies and DNA.

To attach targeting agents:

The nanoparticle surface is modified with attachment points (such as carboxylic acids).
A heterobifunctional linker connects the attachment point to a binding site on the antibody or DNA.

One common chemistry used at nanoComposix is NHS-EDC coupling. This reaction links carboxylic acids to free amines on the biological molecule.

After targeting agents are attached, additional polymers or biomolecules are often added. These prevent non-specific binding to other biological structures in the body.

Delivery

Nanoparticles can carry thousands of drug molecules. These molecules may be embedded within the particle or attached to its surface.

Drug release can be sustained over time or rapid and triggered by environmental changes.

Triggers may include changes in:

pH
Heat
Light
Salts or signaling molecules

When combined with targeting, nanoparticles enable localized drug delivery. This can:

Reduce the total dose required
Improve efficacy
Minimize harmful side effects seen with systemic intravenous delivery

Core/Shell Nanoparticles

One delivery strategy uses core/shell nanoparticles, where the core contains a solid or concentrated liquid drug formulation and the shell controls how quickly the drug diffuses out.

Porous silica shells with controlled thickness allow precise control of drug diffusion rates. The silica surface can also be chemically modified to bind the drug. The large surface area of the porous shell helps hold and gradually release the compound.

More advanced systems can include a trigger mechanism. Drug release occurs only when the trigger is activated, allowing further treatment localization.

Photothermal Treatments

One of the most promising nanoparticle therapies is localized heat generation. Plasmonic nanoparticles can absorb light and convert it into heat. This heat is released into the surrounding tissue.

By adjusting nanoparticle size and shape, the peak absorbance can be tuned into the near-infrared region. Biological tissues are relatively transparent in this range, allowing deeper light penetration.

Gold nanoshell–based plasmonic photothermal therapies are currently in clinical trials for head and neck cancer. A video describing the procedure is here.

Image from nanospectra.com

Sienna Biopharmaceuticals is developing a Silver Plasmonic Therapy for treating acne and permanently removing hair. The technology is based on nanoComposix silver nanoplates that have a peak absorption wavelength tuned to match the skin penetrating lasers used in dermatology clinics.

When particles are introduced into a hair follicle, localized heating can:

Reduce oil production in sebaceous glands
Disrupt hair-producing stem cells

Magnetic nanoparticles can also generate heat. Instead of light, they use an oscillating electromagnetic field to produce heat-inducing eddy currents.

Although magnetic field equipment is complex, this approach can treat areas that are difficult to reach with light.

Circulation Time

For nanotherapies to work effectively, nanoparticles must circulate in the bloodstream long enough to reach their target.

Particles must:

Remain stable and unaggregated
Avoid detection by the immune system

Most nanobiotechnology particles are coated with polyethylene glycol (PEG). PEG improves stability and provides stealth properties that increase circulation time.

When targeting is required, antibodies or other targeting agents are typically attached to the outer PEG layer.

With proper surface engineering, nanoparticles can avoid macrophage uptake and achieve extended circulation.

Fate and Transport

After in-vivo injection, nanoparticles are usually cleared by the liver and spleen.

Clearance often involves:

Opsonization (plasma proteins bind to the particle surface)
Recognition by macrophages
Phagocytosis

Opsonization signals Kupffer cells and other macrophages to remove particles from circulation. Kupffer cells are located in liver blood vessels. They are highly active in clearing particles smaller than 100 nm.

Particles engineered to evade Kupffer cells are often sequestered in the spleen. If particles enter tissues, they may travel to regional lymph nodes for clearance. Very small particles (less than ~10 nm) can also be cleared by the kidneys.

Key factors affecting blood clearance pharmacokinetics include:

Hydrodynamic size and stability
Core size
Core morphology
Surface coating
Surface charge and zeta potential
Protein adsorption

All of these parameters must be optimized to maximize circulation time and minimize toxicity.

Regulation and the FDA

Developing new nanotherapeutics is scientifically and regulatorily complex. It is also time-intensive.

However, nanomedicine has the potential to transform therapeutic treatment. Many companies are currently conducting Phase I and Phase II clinical trials with nanoparticle-based drugs.

Once a nanomedicine shows promise in the lab, the next step is building a design history file. This file documents experiments and supports initial regulatory submissions.

At this stage:

Manufacturing methods must be transferred into a GMP quality system.
Regulatory documentation must be prepared.

nanoComposix has the capability to produce nanomaterials under an ISO 13485:2016 certified Quality Management System, and assist with manufacturing transfer for pre-clinical and clinical studies.