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Receptor-mediated targeted drug or toxin delivery
1Institute of Microbiology AS CR, Vídenská 1083, 142 20 Prague 4, Czech Republic
Abstract:
The new approach to the treatment of cancer or to immunomodulation is drug targeting. Cellular uptake of drugs bound to a targeting carrier or to a targetable polymeric carrier is mostly restricted to receptor-mediated endocytosis. Factors that influence the efficiency of receptor-mediated uptake of targeted drug conjugate are the affinity of the targeting moieties, the affinity and nature of the target antigen, density of the target antigen, the epitope of the target antigen, the type of cell target, the rate of endocytosis, the route of internalization of the ligand-receptor complex, the ability of the drug or toxin to release from its targeted carrier, the ability of the drug or toxin to escape from a vesicular compartment into the cytosol, the affinity of the carrier to the drug and the concentration of the carrier. Targeted chemotherapy is also significantly influenced by the antigenic modulation and/or immunoselection of tumor cells. The binding of drug (toxin) to targetable polymeric carrier considerably decreases unwanted side toxicity.
Insights
Drug targeting enhances cancer treatment and immunomodulation by improving cellular drug uptake. This approach minimizes side toxicity by binding drugs to targetable polymeric carriers, optimizing therapeutic outcomes.
Area of Science:
- Oncology
- Immunology
- Nanotechnology
- Pharmacology
Background:
- Drug targeting represents a novel strategy for cancer treatment and immunomodulation.
- Cellular uptake of drugs conjugated to targeting carriers primarily occurs via receptor-mediated endocytosis.
- Understanding the factors influencing this uptake is crucial for effective drug delivery.
Purpose of the Study:
- To elucidate the key factors governing the efficiency of receptor-mediated endocytosis for targeted drug conjugates.
- To explore how drug targeting impacts tumor cell behavior and therapeutic efficacy.
- To highlight the benefits of polymeric carriers in reducing off-target toxicity.
Main Methods:
- Analysis of factors affecting receptor-mediated endocytosis, including ligand-receptor affinity, antigen characteristics, and cellular uptake dynamics.
- Investigation of drug release and escape mechanisms from vesicular compartments into the cytosol.
- Evaluation of the impact of antigenic modulation and immunoselection on targeted chemotherapy effectiveness.
Main Results:
- Receptor-mediated endocytosis efficiency is influenced by multiple factors: targeting moiety affinity, target antigen properties (affinity, density, epitope), cell type, and internalization route.
- Successful drug delivery depends on efficient drug release from the carrier and escape from endosomes into the cell's cytosol.
- Targeted chemotherapy efficacy is significantly affected by tumor cell antigenic modulation and immunoselection.
Conclusions:
- Drug targeting, particularly using targetable polymeric carriers, significantly reduces unwanted side toxicity in cancer therapy.
- Optimizing drug conjugate design and understanding cellular uptake mechanisms are vital for successful targeted drug delivery.
- This approach holds promise for enhancing cancer treatment and immunomodulation strategies.