Valency and affinity control of aptamer-conjugated nanoparticles for selective cancer cell targeting

Area of Science:

• Nanomedicine
• Biotechnology
• Cancer Therapeutics

Background:

• Nanoparticles (NPs) functionalized with targeting ligands aim for selective cancer cell uptake.
• Overexpressed receptors on cancer cells are targets, but moderate expression on healthy cells causes off-tumor toxicity.
• Multivalent interactions offer potential for increased targeting selectivity due to non-linear responses to receptor density.

Purpose of the Study:

• To investigate the influence of valency, aptamer affinity, and epidermal growth factor receptor (EGFR) density on nanoparticle targeting specificity.
• To explore the interplay of these parameters for enhancing selectivity towards cancer cells.
• To guide the rational design of cancer nanotherapeutics by understanding multivalent interactions.

Main Methods:

• Synthesis of a panel of aptamer-functionalized silica-supported lipid bilayers (SSLBs).
• Systematic study of varying NP valency, aptamer affinity, and target cell receptor (EGFR) density.
• Evaluation of SSLB targeting specificity and selectivity in relation to these parameters.

Main Results:

• An evident interplay exists among NP valency, ligand affinity, and cell receptor density.
• SSLB selectivity towards high-EGFR density cells can be tuned by adjusting these parameters.
• A combination of high-affinity aptamers and low valency SSLBs significantly increased selectivity for high-EGFR cells.

Conclusions:

• Tuning multivalent interactions is crucial for enhancing nanoparticle targeting selectivity.
• Low valency and high aptamer affinity optimize targeting of cancer cells with high EGFR expression.
• These findings advance the rational design of targeted nanomedicines for cancer therapy.