Elongated Particles Show a Preferential Uptake in Invasive Cancer Cells

Area of Science:

• Biomedical Engineering
• Materials Science
• Cancer Therapy

Background:

• Cellular uptake of drug carriers is crucial for targeted cancer therapy.
• Particle physical properties, like shape, can influence cellular interactions and drug delivery efficiency.
• Understanding mechanical influences on particle uptake can enhance therapeutic selectivity.

Purpose of the Study:

• To investigate the hypothesis that elongated particles are preferentially taken up by aggressive cancer cells compared to normal cells.
• To compare the efficacy of elongated versus spherical drug carriers in delivering chemotherapy to different cancer cell aggressiveness levels.
• To explore the role of particle aspect ratio in cellular preference for drug delivery applications.

Main Methods:

• Synthesized elongated polystyrene (PS) particles (0.8-2.4 μm) using heat-induced softening and solvent-based methods.
• Assessed cellular uptake of elongated versus spherical PS particles in aggressive (A375+) and less aggressive (A375-) human melanoma cells.
• Developed elongated, paclitaxel-loaded, biodegradable poly(lactic-co-glycolic) acid (PLGA) particles for drug delivery assessment.

Main Results:

• The heat-induced method yielded more homogenous elongated particles (SD=0.42) than the solvent-based method (SD=0.91).
• Aggressive A375+ cells showed a 10% increase in elongated PS particle uptake versus spherical, while less aggressive A375- cells showed a 25% decrease.
• Elongated drug-loaded PLGA particles demonstrated significantly enhanced cytotoxic effects in aggressive cancer cells compared to less aggressive cells, unlike spherical particles.

Conclusions:

• Particle shape significantly impacts cellular uptake, with elongated particles showing preferential uptake by more aggressive cancer cells.
• Tailoring particle physical properties, specifically aspect ratio, can enhance the selectivity of cancer drug delivery systems.
• These findings offer a promising strategy for developing advanced, targeted cancer therapies with improved efficacy and reduced off-target effects.