Cell internalization kinetics and surface charge accessibility of surface-modified PAMAM dendrimers

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cell Biology

Background:

• Poly(amidoamine) dendrimers (PAMAM) are crucial in drug delivery.
• Surface modification influences PAMAM properties.
• Understanding functionalization's role in cell internalization is vital for optimizing drug delivery systems.

Purpose of the Study:

• To investigate how surface functionalization affects PAMAM dendrimer cell internalization kinetics.
• To compare the internalization of PAMAM dendrimers modified with acetyl, folate, and poly(ethylene glycol) groups.
• To elucidate the relationship between surface charge accessibility and cell uptake.

Main Methods:

• Synthesized and characterized surface-modified PAMAM dendrimers (25% and 50% functionalization).
• Quantified cell internalization kinetics in HEK cells over 6 hours.
• Employed molecular dynamics simulations to analyze surface properties and their correlation with internalization.

Main Results:

• Dendrimers with 25% functionalization showed reduced internalization rates and lower maximum uptake compared to native PAMAM.
• Dendrimers with 50% functionalization exhibited negligible cell internalization.
• Molecular dynamics simulations indicated that solvent accessibility of cationic surface charges, not total charge or size, dictates cell internalization.

Conclusions:

• Surface functionalization significantly modulates PAMAM dendrimer cell internalization.
• Optimal drug delivery requires careful control of surface functionalization to maintain charge accessibility.
• These findings guide the rational design of PAMAM-based nanocarriers for enhanced therapeutic efficacy.