Targeted drug delivery to antigens is a crucial subject for B. Pharm students, covering strategies that direct therapeutics specifically to cells expressing particular antigens. This topic explores antigen selection, ligand–receptor interactions, carrier systems such as antibody–drug conjugates (ADCs), immunoliposomes, nanoparticles, linker chemistry, payload design, pharmacokinetics, biodistribution and immune responses. You will learn analytical methods for characterization, clinical translation issues, and formulation challenges that influence efficacy and safety. Mastery of these concepts supports rational design of targeted therapies, improves therapeutic index, and advances personalized medicine. Now let’s test your knowledge with 30 MCQs on this topic.
Q1. What is the primary goal of targeted drug delivery to antigens?
- Delivering drugs preferentially to cells that express the target antigen
- Maximizing systemic exposure of the drug
- Ensuring drugs are chemically inert
- Increasing off-target tissue accumulation
Correct Answer: Delivering drugs preferentially to cells that express the target antigen
Q2. Which statement best distinguishes active targeting from passive targeting?
- Active targeting uses ligand–antigen interactions while passive targeting relies on physiological phenomena like the EPR effect
- Active targeting only uses nanoparticles, passive targeting uses antibodies
- Passive targeting requires receptor binding, active targeting does not
- There is no difference between active and passive targeting
Correct Answer: Active targeting uses ligand–antigen interactions while passive targeting relies on physiological phenomena like the EPR effect
Q3. Which three components are essential in an antibody–drug conjugate (ADC)?
- Antibody, linker, and cytotoxic payload
- Lipid carrier, surfactant, and dye
- Polymer backbone, macromolecule, and sugar
- Solvent, surfactant, and stabilizer
Correct Answer: Antibody, linker, and cytotoxic payload
Q4. What is the main function of a cleavable linker in targeted drug delivery?
- To enable intracellular release of the payload under specific conditions
- To permanently bind the drug to the carrier
- To increase systemic toxicity
- To prevent antigen recognition
Correct Answer: To enable intracellular release of the payload under specific conditions
Q5. Maleimide chemistry is commonly used to conjugate ADC payloads to which functional group on antibodies?
- Thiol groups on cysteine residues
- Carboxyl groups on aspartate residues
- Amide groups on lysine residues
- Hydroxyl groups on serine residues
Correct Answer: Thiol groups on cysteine residues
Q6. What does the term DAR (drug-to-antibody ratio) describe?
- The average number of drug molecules attached to each antibody molecule
- The dose of antibody per patient body weight
- The ratio of antibody to antigen binding sites on cells
- The degradation rate of the linker in plasma
Correct Answer: The average number of drug molecules attached to each antibody molecule
Q7. Which cytotoxic payload is used in brentuximab vedotin?
- Monomethyl auristatin E (MMAE)
- Maytansinoid DM1
- Doxorubicin
- Paclitaxel
Correct Answer: Monomethyl auristatin E (MMAE)
Q8. Trastuzumab emtansine (T-DM1) contains which payload?
- DM1 (mertansine)
- MMAE
- Camptothecin
- Vincristine
Correct Answer: DM1 (mertansine)
Q9. The Enhanced Permeability and Retention (EPR) effect primarily facilitates which type of targeting?
- Passive targeting of nanoparticles to tumor tissue
- Active receptor-mediated uptake by healthy cells
- Direct antigen–antibody covalent bonding
- Increased renal clearance of drugs
Correct Answer: Passive targeting of nanoparticles to tumor tissue
Q10. What is a key advantage of site-specific conjugation in ADC manufacture?
- Generates homogeneous ADCs with controlled DAR and improved stability
- Eliminates the need for a linker
- Increases nonspecific binding to normal tissues
- Always reduces payload potency
Correct Answer: Generates homogeneous ADCs with controlled DAR and improved stability
Q11. Which Fc-mediated effector functions are commonly associated with therapeutic antibodies?
- Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC)
- RNA interference and DNA methylation
- Membrane fusion and viral entry facilitation
- Passive diffusion and renal excretion
Correct Answer: Antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC)
Q12. Which cellular uptake mechanism is most relevant for internalization of antibody-bound antigens leading to ADC activity?
- Receptor-mediated endocytosis (e.g., clathrin-mediated)
- Simple diffusion across the plasma membrane
- Transcytosis via endothelial cells only
- Extracellular enzymatic activation without uptake
Correct Answer: Receptor-mediated endocytosis (e.g., clathrin-mediated)
Q13. Which property is essential for payload selection in ADC design?
- Extremely high cytotoxic potency (low nM to pM IC50)
- High molecular weight >10 kDa
- Strong hydrophilicity to avoid cell entry
- Ability to cause widespread immune activation
Correct Answer: Extremely high cytotoxic potency (low nM to pM IC50)
Q14. How do noncleavable linkers generally release payload inside target cells?
- Proteolytic degradation of the antibody in lysosomes releases a drug–amino acid complex
- They spontaneously hydrolyze in plasma
- They are cleaved by extracellular proteases before uptake
- They release the payload upon UV light exposure
Correct Answer: Proteolytic degradation of the antibody in lysosomes releases a drug–amino acid complex
Q15. Which factor increases the immunogenicity risk of targeted biologics?
- Use of non-human (murine) antibody sequences
- Humanization of the antibody framework
- Low antigen expression on tumors
- Site-specific conjugation of payloads
Correct Answer: Use of non-human (murine) antibody sequences
Q16. Which characteristic defines an optimal antigen for targeted therapy?
- High, tumor-selective expression with efficient internalization upon antibody binding
- Uniform expression on all normal tissues and tumor cells
- Exclusive intracellular localization with no surface expression
- Rapid shedding into circulation to increase exposure
Correct Answer: High, tumor-selective expression with efficient internalization upon antibody binding
Q17. Which stimulus-responsive linker is designed to release payload in acidic endosomal/lysosomal compartments?
- pH-sensitive hydrazone or acetal linkers
- Non-degradable polyethylene linkers
- UV-cleavable nitrobenzyl linkers used systemically
- Stable amide linkers that never cleave
Correct Answer: pH-sensitive hydrazone or acetal linkers
Q18. Which analytical technique is most suitable for accurate determination of DAR distribution?
- Mass spectrometry (e.g., LC–MS)
- UV-visible spectroscopy alone
- Simple gel electrophoresis without detection
- Light microscopy
Correct Answer: Mass spectrometry (e.g., LC–MS)
Q19. What is the primary purpose of PEGylation in targeted nanoparticle formulations?
- To increase circulation time and reduce opsonization
- To increase antigenicity of the carrier
- To promote immediate renal clearance
- To prevent ligand–receptor interactions
Correct Answer: To increase circulation time and reduce opsonization
Q20. What defines a heterobifunctional linker used in conjugation chemistry?
- A linker with two different reactive groups that can react with distinct functional groups on payload and carrier
- A linker that contains identical reactive groups on both ends
- A linker that prevents any chemical reactions
- A linker composed solely of polyethylene glycol
Correct Answer: A linker with two different reactive groups that can react with distinct functional groups on payload and carrier
Q21. What are immunoliposomes?
- Liposomes decorated with antibodies or antibody fragments for targeted delivery
- Liposomes that only contain immune adjuvants without targeting
- Antibodies physically trapped inside liposomes without surface display
- Liposomes that target bacteria via lipid A interaction
Correct Answer: Liposomes decorated with antibodies or antibody fragments for targeted delivery
Q22. Bispecific antibodies can be designed to do which of the following in cancer therapy?
- Redirect T cells to tumor cells by binding CD3 and a tumor antigen simultaneously
- Bind only to two identical epitopes on the same antigen
- Function solely as enzyme inhibitors
- Replace the need for linkers in ADCs
Correct Answer: Redirect T cells to tumor cells by binding CD3 and a tumor antigen simultaneously
Q23. ADC plasma stability is most strongly influenced by which factors?
- Linker stability and conjugation site on the antibody
- Color of the formulation and vial size
- Route of administration alone without chemistry considerations
- Patient age only
Correct Answer: Linker stability and conjugation site on the antibody
Q24. The mechanism of action of auristatin payloads primarily involves:
- Inhibition of microtubule polymerization leading to mitotic arrest
- Intercalation into DNA to cause strand breaks
- Topoisomerase II inhibition
- Induction of lipid peroxidation in membranes
Correct Answer: Inhibition of microtubule polymerization leading to mitotic arrest
Q25. A major challenge for antigen-targeted therapies in solid tumors is:
- Heterogeneous antigen expression leading to incomplete target coverage and resistance
- Uniform overexpression of antigen on all tumor cells
- The inability of antibodies to bind any cell surface proteins
- Excessively rapid diffusion into tumor core improving efficacy
Correct Answer: Heterogeneous antigen expression leading to incomplete target coverage and resistance
Q26. What nanoparticle size range is generally considered optimal to exploit the EPR effect for tumor targeting?
- Approximately 10–200 nm
- Less than 1 nm
- Greater than 1,000 nm
- Exactly 5000 nm
Correct Answer: Approximately 10–200 nm
Q27. How does targeted delivery typically affect the therapeutic index of a drug?
- Increases the therapeutic index by raising target exposure and lowering off-target toxicity
- Always decreases the therapeutic index
- Has no impact on therapeutic index
- Makes the drug universally non-toxic
Correct Answer: Increases the therapeutic index by raising target exposure and lowering off-target toxicity
Q28. Disulfide linkers in ADCs are commonly cleaved intracellularly by which mechanism?
- Reduction by intracellular glutathione or other reducing agents
- Cleavage by extracellular proteases in plasma
- Direct hydrolysis by neutral pH in plasma
- Cleavage by visible light exposure
Correct Answer: Reduction by intracellular glutathione or other reducing agents
Q29. Which experimental method is commonly used to quantify cell-surface antigen expression and antibody binding on cells?
- Flow cytometry
- X-ray crystallography
- Gas chromatography
- Ultracentrifugation
Correct Answer: Flow cytometry
Q30. Which regulatory consideration is critical for approval of ADC therapeutics?
- Demonstration of consistent manufacturing, characterization of DAR, impurity profiles and stability
- Only demonstrating color consistency of the final vial
- No requirement for pharmacokinetic or safety data
- Approval without any clinical efficacy evidence
Correct Answer: Demonstration of consistent manufacturing, characterization of DAR, impurity profiles and stability
I am a Registered Pharmacist under the Pharmacy Act, 1948, and the founder of PharmacyFreak.com. I hold a Bachelor of Pharmacy degree from Rungta College of Pharmaceutical Science and Research. With a strong academic foundation and practical knowledge, I am committed to providing accurate, easy-to-understand content to support pharmacy students and professionals. My aim is to make complex pharmaceutical concepts accessible and useful for real-world application.
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