Advancements in folate receptor targeting for anti-cancer therapy: A small molecule-drug conjugate approach

Area of Science:

• Oncology
• Pharmacology
• Drug Delivery

Background:

• Cancer therapies often harm healthy cells due to non-specific drug distribution.
• Personalized medicine demands targeted drug delivery and controlled release systems.
• Small molecule-drug conjugates (SMDCs) represent a promising approach to enhance therapeutic efficacy and minimize side effects.

Purpose of the Study:

• To review the principles, advantages, and drawbacks of designing small molecule-drug conjugates (SMDCs).
• To summarize the essential criteria for developing effective SMDCs for cancer treatment.
• To discuss SMDC components, including targeting ligands, linkers, spacers, and payloads, with a focus on folate receptor targeting.

Main Methods:

• Literature review of SMDC design principles and criteria.
• Analysis of SMDC components: targeting ligands, releasable bridges, spacers, and payloads.
• Discussion of linker chemistries, cleavage strategies, and receptor selection for tumor targeting.
• Review of folate receptor-targeting SMDCs in preclinical and clinical development.

Main Results:

• Effective SMDC design requires careful selection of tumor-specific receptors and optimal molecular components.
• Linker chemistry and cleavage strategies are critical for controlled drug release at the target site.
• Folate receptor-targeting SMDCs show potential in preclinical and clinical settings.

Conclusions:

• SMDCs are a key strategy for achieving potent anticancer effects with reduced systemic toxicity.
• Optimized design of SMDCs, considering all components and targeting strategies, is crucial for successful clinical translation.
• Further development of SMDCs, particularly those targeting specific receptors like the folate receptor, holds significant promise for personalized cancer therapy.