Biological events involved in targeting MCQs With Answer

Biological events involved in targeting MCQs With Answer provides M. Pharm students a focused, exam-ready dive into the mechanistic journey of targeted drug delivery systems in vivo. From circulation and opsonization to extravasation, receptor-mediated uptake, intracellular trafficking, and triggered release, these events determine whether nanocarriers reach their intended site and act effectively. This quiz emphasizes critical determinants such as size, surface charge, protein corona, RES clearance, EPR effect, and the role of ligand–receptor biology. You will also revisit concepts of endosomal escape, complement activation, BBB transcytosis, and tumor microenvironment-responsive mechanisms. Designed to test conceptual clarity and practical reasoning, these MCQs help bridge molecular pharmaceutics principles with translational outcomes in NTDS.

Q1. Which sequence best represents the in vivo cascade after IV injection of a ligand-targeted nanocarrier aiming at tumor cells?

• Circulation → protein corona formation/opsonization → extravasation (EPR) → interstitial transport → receptor binding → endocytosis → intracellular trafficking → payload release
• Receptor binding → circulation → interstitial transport → extravasation → endocytosis → release → opsonization
• Extravasation → circulation → opsonization → receptor binding → release → trafficking
• Endocytosis → receptor binding → circulation → release → extravasation

Correct Answer: Circulation → protein corona formation/opsonization → extravasation (EPR) → interstitial transport → receptor binding → endocytosis → intracellular trafficking → payload release

Q2. What is the principal impact of the protein corona on actively targeted nanoparticles?

• It masks ligands and redirects biodistribution via opsonins, diminishing targeting specificity
• It enhances ligand exposure and increases receptor affinity
• It increases glomerular filtration independent of size
• It completely prevents complement activation

Correct Answer: It masks ligands and redirects biodistribution via opsonins, diminishing targeting specificity

Q3. The primary biological rationale for PEGylating nanocarriers is to:

• Reduce opsonization and RES clearance to extend circulation half-life
• Increase lysosomal degradation after cell uptake
• Accelerate renal clearance by shrinking hydrodynamic diameter
• Improve receptor affinity of attached ligands

Correct Answer: Reduce opsonization and RES clearance to extend circulation half-life

Q4. Efficient glomerular filtration typically occurs for solutes or particles with a hydrodynamic diameter approximately:

• ≲ 5–6 nm (≈ 40–60 kDa proteins)
• 20–50 nm
• 100–200 nm
• ≥ 300 nm

Correct Answer: ≲ 5–6 nm (≈ 40–60 kDa proteins)

Q5. The Enhanced Permeability and Retention (EPR) effect refers to:

• Passive accumulation of carriers in tumors due to leaky vasculature and poor lymphatic drainage
• Active uptake mediated by high-affinity ligands on tumor cells
• Rapid renal excretion of hydrophilic macromolecules
• Absorption enhancement across the intestinal mucosa

Correct Answer: Passive accumulation of carriers in tumors due to leaky vasculature and poor lymphatic drainage

Q6. Which surface attribute most increases non-specific cell uptake and rapid plasma protein adsorption?

• Highly cationic zeta potential (> +20 mV)
• Near-neutral, hydrated surface
• Dense PEG brush
• Low polydispersity index

Correct Answer: Highly cationic zeta potential (> +20 mV)

Q7. Ligand binding to LDL or transferrin receptors on the cell surface is predominantly internalized via:

• Clathrin-mediated endocytosis
• Caveolae-mediated endocytosis
• Macropinocytosis
• Phagocytosis

Correct Answer: Clathrin-mediated endocytosis

Q8. The “proton sponge” mechanism facilitating endosomal escape is most associated with:

• Polyethylenimine (PEI) enabling endosomal buffering and rupture
• Poly(ethylene glycol) (PEG) imparting steric stabilization
• PLGA enhancing hydrolytic degradation
• Gold nanoparticles inducing photothermal effects

Correct Answer: Polyethylenimine (PEI) enabling endosomal buffering and rupture

Q9. Increasing ligand density on a nanoparticle often results in:

• Higher avidity but potential binding-site barrier that reduces deep tumor penetration
• Unlimited improvement in tumor penetration
• No change in binding or distribution
• Elimination of the need for EPR-mediated access

Correct Answer: Higher avidity but potential binding-site barrier that reduces deep tumor penetration

Q10. The key distinction between passive and active targeting is that:

• Active targeting relies on specific ligand–receptor interactions; passive targeting depends on physiological features like the EPR effect
• Passive targeting uses ligands; active targeting does not
• Active targeting avoids endocytosis; passive targeting causes endocytosis
• Passive targeting requires stimuli-responsive materials; active targeting does not

Correct Answer: Active targeting relies on specific ligand–receptor interactions; passive targeting depends on physiological features like the EPR effect

Q11. A receptor commonly exploited for receptor-mediated transcytosis (RMT) across the blood–brain barrier is:

• Transferrin receptor (TfR)
• Dopamine D2 receptor
• GABA-A receptor
• Histamine H1 receptor

Correct Answer: Transferrin receptor (TfR)

Q12. Which cell type is a principal mediator of opsonized nanoparticle clearance from blood?

• Kupffer cells (hepatic macrophages) in the liver
• Podocytes in the kidney
• Neurons in the CNS
• Enterocytes in the intestine

Correct Answer: Kupffer cells (hepatic macrophages) in the liver

Q13. Which strategy best enables nanoparticles to diffuse through mucus for effective targeting beyond the mucosal barrier?

• Creating a dense, low–molecular-weight PEG brush to make a muco-inert surface
• Introducing high positive charge to stick to mucins
• Increasing hydrophobicity to promote adhesion
• Using large particles (>500 nm) to avoid entrapment

Correct Answer: Creating a dense, low–molecular-weight PEG brush to make a muco-inert surface

Q14. Complement activation-related pseudoallergy (CARPA) is primarily mediated by:

• Generation of anaphylatoxins C3a and C5a upon complement activation by the carrier
• Direct mast cell degranulation by PEG chains
• Insufficient ligand density on the nanoparticle
• Exclusively IgE-mediated hypersensitivity

Correct Answer: Generation of anaphylatoxins C3a and C5a upon complement activation by the carrier

Q15. Which property most enhances margination of particles toward the endothelium in microcirculation?

• Non-spherical (discoidal/rod-like) shapes and larger submicron-to-micron sizes
• Very small (~5 nm) spherical particles
• Highly negative zeta potential alone
• High material density without changing size or shape

Correct Answer: Non-spherical (discoidal/rod-like) shapes and larger submicron-to-micron sizes

Q16. Which chemical linker is most suitable for intracellular, reductive environment-triggered drug release?

• Disulfide bond (–S–S–) cleavable by cytosolic glutathione
• Stable amide linkage resistant to cytosolic reduction
• Ether linkage
• Siloxane bond

Correct Answer: Disulfide bond (–S–S–) cleavable by cytosolic glutathione

Q17. pH-sensitive carriers designed for endosomal release generally respond to the pH range of:

• Approximately 5.0–5.5
• 7.2–7.4
• 8.0–8.5
• 2.0–3.0

Correct Answer: Approximately 5.0–5.5

Q18. High-affinity, rapidly internalizing ligands can produce which effect during repeated dosing?

• Receptor downregulation after endocytosis, reducing subsequent uptake
• Upregulation of receptor density, increasing uptake indefinitely
• No change in receptor trafficking dynamics
• Complete avoidance of lysosomal routing

Correct Answer: Receptor downregulation after endocytosis, reducing subsequent uptake

Q19. Rigid particles larger than which approximate size risk mechanical entrapment in splenic interendothelial slits?

• ≈ 200–300 nm and above (if non-deformable)
• < 10 nm
• ≈ 50 nm
• > 5 μm only

Correct Answer: ≈ 200–300 nm and above (if non-deformable)

Q20. For an EPR-dependent nanomedicine, which pharmacokinetic change most improves the probability of tumor accumulation?

• Prolonged circulation half-life (increased AUC) without excessive off-target interactions
• High Cmax with ultrashort half-life
• Increased systemic clearance
• Extremely large volume of distribution into non-target tissues

Correct Answer: Prolonged circulation half-life (increased AUC) without excessive off-target interactions

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