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What is one effect of the protein corona on nanoparticles?
Coating nanoparticles with polyethylene glycol (PEG) increases their chances of being recognized by immune cells.
False
What is the main purpose of coating nanoparticles with 'don't eat-me' markers like CD47?
To prevent their recognition and removal by the immune system.
The ______________ is responsible for the clearance of nanoparticles from circulation by immune cells.
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Which characteristic of nanoparticles can be influenced by the protein corona formation?
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Match the following nanoparticle coatings with their intended effects:
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Activation of the immune system through nanoparticle opsonization can lead to beneficial effects only.
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What adverse effects can result from the activation of the immune system by nanoparticles?
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What is the ideal size for nanoparticles to avoid opsonization and clearance by the immune system?
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The Enhanced Permeability and Retention (EPR) effect is present in all types of tumors.
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What mechanism allows nanoparticles to enter tumor tissue?
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The optimal particle size for cellular uptake of gold nanoparticles is a result of competing factors, specifically membrane wrapping and __________ kinetics.
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Match the following nanoparticle characteristics with their impacts:
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Which of the following factors does NOT affect cellular uptake of nanoparticles?
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Nanoparticles are more likely to be cleared by the mononuclear phagocyte system if they are larger than 200 nm.
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What is one characteristic of nanoparticles that influences their interaction with cells?
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Which of the following is NOT a key characteristic of nanoparticles for medical applications?
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Nanoparticles must have a minimum side effect for in vitro applications.
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What is one method by which nanoparticles can be synthesized?
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The process by which a cell membrane loses its rigidity and undergoes changes due to attached nanoparticles is called __________.
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What is the impact of positively charged Au nanospheres on negatively charged cell surfaces?
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Match the nanoparticle properties with their effects:
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What do MnO nanoparticles enhance in T1-weighted MRI for detecting breast cancer cells?
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Gold nanorods are used to transfer thermal energy to cardiac tissues.
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Study Notes
Shape-Dependent Cellular Uptake of Gold Nanoparticles
- Positively charged gold nanospheres attached to negatively charged cell surfaces trigger endocytosis to maintain the original charge distribution.
- This results in changes to membrane fluidity and permeability.
Key Characteristics of Nanoparticles for Medical Applications
- Size and surface area of nanoparticles
- Polydispersity
- Shape of nanoparticles (spherical, cube, triangle, rod)
- Surface charge
- Materials type (gold, iron oxide, polymer)
- Protein-nanoparticles interaction
- Toxicity, clearance, or minimum side effect (in vivo applications)
Disease Diagnosis
- Water-dispersible MnO nanoparticles are used for in vivo MRI.
Imaging Selectively the Breast Cancer Cells in the Metastatic Brain Tumor Model Using MnO Nanoparticles (T1-weighted MRI)
- 15 nm MnO nanoparticles functionalized with tumor-specific antibodies are delivered to and accumulate in cancer cells, enhancing them in T1-weighted MRI.
Gold Nanorod-Based Engineered Cardiac Patch for Suture-Free Engraftment by Near IR
- Gold nanorods absorbs light and convert it into thermal energy, which locally changes the molecular structure of the fibrous scaffold.
- This allows for a strong, but safe attachment to the heart wall without sutures.
Nanomaterials Show Size and Shape Dependent Physical Properties
- Nanomaterials are synthesized using top-down and bottom-up approaches.
- The performance of nanomaterials depends on their interactions with biological species.
- Nanotechnology has revolutionized approaches to diagnosing treating and preventing cancerous and non-cancerous diseases.
Protein Corona/Opsonization
- The formation of a protein corona (opsonization) around nanoparticles can alter:
- Physicochemical properties of NPs (size, shape, surface charge, hydrophobicity), impacting cellular uptake, toxicity, and clearance.
- Recognition by immune cells, such as the mononuclear phagocyte system (MPS), leading to their removal from circulation.
- Activation of the immune system, resulting in production of inflammatory cytokines and adverse effects like inflammation, fever, or allergic reactions.
- Masking of targeting ligands, reducing the specificity and efficacy of drug delivery or imaging agent targeting.
Strategies to Overcome Protein Corona/Opsonization and MPS Clearance
-
Coating nanoparticles with polyethylene glycol (PEG):
- Ethylene glycol forms tight associations with water molecules, creating a hydrating layer that hinders protein corona formation.
- Increases circulation time.
-
Coating nanoparticles with:
- "Don't eat me" marker CD47:
- Reduces opsonization
- Prolongs circulation
- Inhibits MPS clearance
- Enhances delivery
- "Self" peptides:
- Reduces opsonization
- Prolongs circulation
- Inhibits MPS clearance
- Enhances delivery
- "Don't eat me" marker CD47:
-
Coating nanoparticles with red blood cell (RBC) membranes (rich in proteins, such as CD47 and glycophorin A):
- Decreases opsonization
- Enhances circulation
- Non-immunogenic and non-fouling, avoiding recognition by immune cells and MPS clearance.
-
Leukocyte membrane-coated nanoparticles produce similar effects to RBC-coated nanoparticles, camouflaging them.
Strategies to Overcome Clearance of NPs
- NPs larger than 200 nm are more likely to activate reactions that lead to opsonization and clearance by phagocytes.
- Target size should be below 200 nm to overcome this challenge.
Mononuclear Phagocyte System (MPS)
- Phagocytic cells (macrophages and neutrophils) that engulf and remove particulate matter from the bloodstream.
- Plays a critical role in immune surveillance, but can also lead to clearance of nanoparticles if not properly addressed.
Nanoparticles Entry to Solid Tumor: Enhanced Permeability and Retention (EPR) Effect
- Passive targeting mechanism that exploits leaky vasculature in tumor tissue due to uncontrolled growth of tumor cells.
- This leakiness allows nanoparticles to cross blood vessel walls that they would not normally be able to.
- Gap size is approximately 100-500 nm, as opposed to the tight junctions of healthy tissue.
- EPR effect is not universal and dependent on tumor type, size, and location.
Nanomaterials-Cell Interaction
- Nanoparticles are used for intracellular drug delivery.
- Interactions with cells depend on size, shape, surface charge, and materials property (soft or stiff).
Size-Dependent Cellular Uptake of Gold Nanoparticles
- The optimal particle diameter for the smallest internalization time is determined by a competition between thermodynamic driving forces of membrane wrapping (receptor binding) and receptor diffusion kinetics (receptor recruitment).
- Transmission electron microscopy imaging and measurements of gold nanoparticles in cells show a correlation between nanoparticle size and intracellular localization.
Size-Dependent Cellular Uptake of Gold Nanoparticles: Observations
- Incubation of HeLa cells with gold nanoparticles of various sizes led to the following findings:
- There is an optimal particle diameter for the smallest internalization time.
- TEM images show gold nanoparticles of various sizes (14, 30, 50, 74, and 100 nm) trapped inside vesicles of HeLa cells.
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Description
Explore the fascinating role of nanoparticles in medical applications, focusing on their shape-dependent cellular uptake, key characteristics, and use in disease diagnosis. This quiz covers various types of nanoparticles and their interactions with biological systems, particularly in imaging techniques like MRI for cancer detection.
