Nanobiotechnology applies nanoscale materials and engineering principles to biological and medical systems. Nanomedicine is one important part of this broader field, using nanoparticles and other engineered materials for applications such as drug delivery, imaging, targeting, sensing, and externally activated therapies.
Nanoparticle behavior in biological systems can be tuned through particle size, shape, composition, surface chemistry, charge, porosity, optical properties, and biodegradability. These variables influence how a particle carries or releases a payload, interacts with biomolecules and cells, moves through biological environments, and is ultimately cleared.
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How Nanoparticles Are Engineered for Biological Systems
Nanoparticles can be designed to perform different functions depending on the intended application. Examples include:
- Carrying and releasing therapeutic compounds
- Providing optical, fluorescent, magnetic, or other imaging signals
- Presenting antibodies, peptides, oligonucleotides, or other biomolecules at the particle surface
- Responding to external stimuli such as light or magnetic fields
- Controlling interactions with proteins, cells, tissues, and biological fluids
Many systems combine several of these functions within a single particle. A nanoparticle might, for example, carry a therapeutic payload while also presenting a targeting ligand or providing an imaging signal.
Nanoparticle Targeting & Surface Engineering
Surface chemistry plays a central role in determining how nanoparticles interact with biological environments. Antibodies, peptides, oligonucleotides, and other recognition molecules can be attached to the nanoparticle surface to promote interactions with selected molecular or cellular targets.
Passive Accumulation
Nanoparticles can sometimes accumulate preferentially in particular tissues because of physiological differences in vasculature, permeability, lymphatic transport, or clearance. The enhanced permeability and retention (EPR) effect has been studied extensively as one mechanism for nanoparticle accumulation in tumors.
However, passive accumulation varies substantially among tumor types, animal models, patients, particle designs, and disease states. Particle size alone does not determine whether a nanoparticle will accumulate effectively at a target site.
Active Targeting
Active targeting uses molecules at the nanoparticle surface to promote recognition of selected receptors, cells, or biological structures. Examples include antibodies, antibody fragments, peptides, aptamers, and oligonucleotides.
A common conjugation strategy begins with a carboxyl-functionalized nanoparticle. EDC/NHS chemistry can activate the carboxyl groups for reaction with primary amines on a protein or other biomolecule, forming a covalent amide bond.
Targeting ligands primarily influence interactions after a nanoparticle encounters the relevant biological environment. Effective delivery still depends on broader factors such as circulation, tissue transport, particle stability, protein adsorption, and accessibility of the biological target.
For additional conjugation approaches, see Custom Conjugate Development & Manufacturing and our Nanoparticle Conjugation Protocols.
Nanoparticles for Controlled Drug Delivery
Nanoparticles can carry therapeutic molecules by encapsulating them within a particle matrix or pore network, incorporating them into a core or shell, adsorbing them to a surface, or attaching them through chemical linkages.
The appropriate architecture depends on the payload and desired release behavior. Important design variables can include particle size, matrix composition, molecular weight, porosity, pore size, surface chemistry, payload affinity, degradation rate, and processing conditions.
Release may be designed to occur gradually over time or to respond to changes in the surrounding environment. Depending on the platform, release mechanisms can involve diffusion, degradation, desorption, or responses to variables such as pH, temperature, or externally applied energy.
Polymeric Nanoparticles
Biodegradable polymers such as PLGA can encapsulate therapeutic payloads within a polymer matrix. Polymer composition, molecular weight, end-group chemistry, particle size, and formulation conditions can be adjusted to influence payload loading and release behavior.
Learn more about Custom PLGA Particle Development and Engineering Polymer Particle Platforms for Precision Delivery.
Mesoporous Silica
Mesoporous silica nanoparticles provide an internal pore network with high accessible surface area. Pore dimensions, architecture, and surface chemistry can be tailored around the size and chemical properties of a payload, while the exterior surface can be modified independently for additional functionality.
Explore Mesoporous Silica Nanoparticles or read Enhancing Therapeutic Delivery with Tunable Mesoporous Silica Nanoparticle Platforms.
Photothermal & Magnetothermal Applications
Some nanoparticles can convert externally applied energy into localized heat. Plasmonic nanoparticles such as gold nanoshells, gold nanorods, and silver nanostructures can absorb selected wavelengths of light and convert that optical energy into heat.
Particle geometry provides control over the absorption wavelength, allowing plasmonic structures to be designed around specific laser wavelengths. Near-infrared-responsive particles are especially relevant when greater optical penetration through tissue is required.
Gold-silica nanoshell platforms have progressed into human clinical research for light-activated thermal ablation, demonstrating the translational potential of plasmonic photothermal nanomaterials.
Historical clinical research example using gold-silica nanoshell technology. Image from Nanospectra.
Topical Photothermal Systems
nanoComposix has also developed plasmonic particles for topical photothermal applications. In one program, silica-shelled silver nanoplates were engineered with optical absorption matched to a near-infrared dermatology laser and developed as a component of a topical treatment platform.
Particles delivered into the follicular region can absorb laser energy and generate localized heating. Programs using this approach have investigated applications including modulation of sebaceous glands for acne treatment and disruption of hair-producing structures for hair removal.
See Photothermal Applications of Nanoparticles and our Photothermal Nanoparticle Case Study for more detail.
Magnetic Heating
Magnetic nanoparticles can also generate heat when exposed to an alternating magnetic field. Unlike optical approaches, magnetic-field penetration is not limited by the same tissue optical attenuation, making magnetic heating useful for different classes of biomedical research.
Particle composition, magnetic properties, size, concentration, and applied-field conditions all influence heating performance.
Circulation Time & Biological Interactions
For intravenously administered nanoparticles, circulation time can strongly influence biodistribution and the opportunity for a particle to reach its intended tissue. Particle behavior in blood is affected by size, surface chemistry, charge, colloidal stability, and interactions with proteins and other biomolecules.
When nanoparticles enter biological fluids, proteins and other biomolecules can adsorb to their surface and form a biomolecular corona. This new interface can affect recognition by cells, circulation, aggregation, targeting interactions, and clearance.
Hydrophilic polymer coatings such as polyethylene glycol (PEG) are commonly used to modify these interactions. PEG can provide steric stabilization and reduce some nonspecific protein adsorption, although its biological effects depend on variables such as polymer molecular weight, surface density, nanoparticle properties, and administration context.
Targeting ligands can also be presented at or beyond the polymer layer when receptor-specific interactions are required.
Nanoparticle Fate, Biodistribution & Clearance
After systemic administration, nanoparticles encounter a sequence of biological barriers that can influence where they distribute and how rapidly they are removed from circulation.
The liver and spleen are important sites of accumulation and clearance for many nanoparticle systems. Protein adsorption and subsequent recognition by cells of the mononuclear phagocyte system can contribute to uptake by macrophages, including Kupffer cells in the liver.
Very small nanoparticles may also undergo renal clearance, but there is no single particle-diameter cutoff that applies to every material. Renal filtration depends on hydrodynamic size as well as particle shape, surface chemistry, charge, flexibility, protein adsorption, and other biological interactions.
Important determinants of nanoparticle biodistribution and pharmacokinetics include:
- Hydrodynamic size and colloidal stability
- Core size and morphology
- Surface chemistry and coating density
- Surface charge
- Protein adsorption and biomolecular-corona formation
- Particle degradation and dissolution
- Route of administration
- Dose and concentration
These properties need to be evaluated together because changing one nanoparticle parameter can alter several biological interactions simultaneously.
Translating Nanomedicine from Development to Manufacturing
Nanomedicine development requires control of both the therapeutic formulation and the nanoparticle manufacturing process. As a program progresses from feasibility through preclinical and clinical development, requirements for characterization, reproducibility, process control, documentation, and material qualification typically increase.
Development programs may need to establish and control parameters such as:
- Critical particle and formulation attributes
- Raw material specifications
- Manufacturing process parameters
- Analytical methods and acceptance criteria
- Payload loading and release characteristics
- Impurities and residual process components
- Stability and storage conditions
- Batch records and manufacturing documentation
- Scale-up and process reproducibility
The applicable regulatory pathway depends on the finished product, intended use, and whether the system is regulated as a drug, biologic, medical device, combination product, or another product type. Nanomaterial-specific properties may require additional characterization and consideration as part of product development.
Research vs. clinical development: Standard nanoComposix catalog materials are supplied for research use. Programs intended for preclinical, clinical, or regulated applications require project-specific development, qualification, manufacturing controls, and regulatory assessment.
nanoComposix supports programs from early formulation feasibility through process development, scale-up, technology transfer, and regulated manufacturing within the scope of our quality systems.
Nanomedicine Development at nanoComposix
Publicly documented nanoComposix development programs illustrate the range of nanoparticle technologies used in translational nanomedicine, including:
- PLGA nanoparticle development and GMP manufacturing for an immunotherapy program
- Mesoporous silica development and large-scale process translation for a cancer therapeutic
- Silica-coated magnetic nanoparticles with antibody targeting for tumor-directed magnetic heating
- Oligonucleotide-conjugated gold nanoparticles for therapeutic development
- Topical plasmonic nanoparticles developed and transferred into GMP manufacturing for photothermal applications
- Gold nanoparticle conjugates developed as therapeutic and pharmacokinetic platforms
Explore additional examples on our Nanoparticle Development Case Studies page.
Developing a nanoparticle-based therapeutic?
Talk with our technical team about particle design, payload loading, conjugation, characterization, formulation optimization, process development, scale-up, or manufacturing strategy.
Selected Literature
Research Featuring nanoComposix Nanoparticles
- Fuller, M.; Whiley, H.; Köper, I. Antibiotic Delivery Using Gold Nanoparticles. SN Applied Sciences 2020, 2, 1022.
Nanoparticle Design & Biological Interactions
- Blanco, E.; Shen, H.; Ferrari, M. Principles of Nanoparticle Design for Overcoming Biological Barriers to Drug Delivery. Nature Biotechnology 2015, 33, 941–951.
- Monopoli, M. P.; Åberg, C.; Salvati, A.; Dawson, K. A. Biomolecular Coronas Provide the Biological Identity of Nanosized Materials. Nature Nanotechnology 2012, 7, 779–786.
- Wilhelm, S.; Tavares, A. J.; Dai, Q.; et al. Analysis of Nanoparticle Delivery to Tumours. Nature Reviews Materials 2016, 1, 16014.
Related nanomedicine resources