A prototypical nanoparticle is produced by chemical synthesis, then co

A prototypical nanoparticle is produced by chemical synthesis, then coated with polymers, drugs, fluorophores, peptides, proteins, or oligonucleotides, and eventually administered into cell cultures. Nanoparticles were conceived of as benign carriers, but multiple studies have demonstrated that their design influences cell uptake, gene expression, and toxicity.

More specifically, interactions between nanoparticle-bound ligands (the molecules that bind to nanoparticles) and cellular receptors depend on the engineered geometry and the ligand density of a nanomaterial. The nanoparticle acts as a scaffold whose design dictates the number of ligands that interact with the receptor target. A multivalent effect occurs when multiple ligands on the nanoparticle interact with multiple receptors on the cell. The binding strength of complexed ligands is more than the sum of individual affinities; the accumulated effect of multiple affinities is known as the avidity for the entire complex.

This phenomenon is illustrated by the binding affinity of the antibody trastuzumab to the ErbB2 receptor, a protein whose overexpression has been shown to play an important role in the development and progression of certain aggressive types of breast cancer. Trastuzumab's binding affinity to ErbB2 when liganded to a nanoparticle increases proportionally with the size of a nanoparticle, owing to a higher density of the ligand on the nanoparticle surface. However, when viewed in terms of the downstream signaling via the ErbB2 receptor, mid-sized gold nanoparticles induced the strongest effect, suggesting that factors beyond binding affinity must be considered.

Furthermore, several studies have shown that nanoparticle design can generate effects not obtained simply by a free ligand in solution. For example, the aforementioned mid-sized trastuzumab-coated gold nanoparticles altered cellular apoptosis, the process of programmed cell death, by influencing the activation of the so-called "executioner" caspase enzymes. Similarly, receptor-specific peptides improved their ability to induce angiogenesis, the physiological process through which new blood vessels form from preexisting vessels, when these peptides are conjugated to a nanoparticle surface. Specifically, presentation of the peptide on a structured scaffold increased angiogenesis, which is dependent on receptor-mediated signaling. These findings highlight the advantages of a ligand bound to a nanoparticle over one free in solution. The nanoparticle surface creates a region of highly concentrated ligand, which increases avidity and, potentially, alters cell signaling.

1. Which of the following titles best summarizes the contents of the passage?

A. Nanoparticles: Their Critical Function in Cell Signaling
B. Nanoparticles and Ligands: A Myth Debunked
C. Nanoparticles and Ligands: A Reciprocal Dependence
D. Factors Influencing the Affinity Between Nanoparticles and Free Ligands
E. The Effects of Nanoparticle Design on Ligands' Avidity and Cell Signaling

2. According to the passage, the binding affinity of an nanoparticle-bound ligand to a receptor typically

A. increases with the size of the nanoparticle
B. is unrelated to the shape of the nanoparticle
C. has unintended cell signaling effects
D. accelerates the death of that receptor
E. is less effective than the free ligand in solution

3. According to the passage, when the scientists first began the design and construction of nanoparticles, they knew that

A. further research would be required to determine nanoparticle effects
B. factors beyond binding affinity would affect the design
C. nanoparticles would have multivalent effects
D. nanoparticles would alter cell signaling
E. ligands would bind to nanoparticles

4. In citing "factors beyond binding affinity" in the highlighted text, the author is referring to factors that most likely include which of the following?

A. The cost of nanoparticle production
B. Nanoparticle signals known to contribute to aggressive cancers
C. Positive effects that do not increase proportionally with a nanoparticle's size
D. Unintended, harmful cell signaling caused by nanoparticles
E. The exact mechanism by which conjugation to a nanoparticle surface occurs

5. According to the passage, nanoparticle-bound ligands have the ability to

A. combat cancer cells as effectively as a much higher concentration of free ligands
B. influence both the creation and the destruction of cells and tissues
C. generate effects that cannot be obtained those same ligands without nanoparticles
D. affect the number of possible interaction types between an antibody and a receptor
E. regenerate ligands that have experienced apoptosis

6. The author's discussion of the "peptide on a structured scaffold" mentioned in the highlighted text is intended to

A. stimulate further research studies
B. summarize an area of scientific investigation
C. give an example of the type of phenomenon under discussion
D. provide supporting evidence for a controversial scientific theory
E. refute the conclusions of a previously mentioned research study

7. With which of the following statements about nanoparticles would the author most likely agree?

A. They represent the best available means to treat certain aggressive types of cancer.
B. They have an unreliable effect.
C. They pose risks that are underappreciated.
D. They have applications that were not originally foreseen.
E. They will generally have contradictory effects on cell death.

8. It can be inferred from the passage that which of the following would be part of the best approach to develop a new therapy using nanoparticles?

A. Exploring nanoparticle design
B. Using a hybrid application of bound and free ligands
C. Developing larger nanoparticles
D. Maximizing binding affinity
E. Minimizing receptor-mediated signaling