Nanocomplexes of Biodegradable Anticancer Macromolecules: Prolonged Plasma Half-Life, Reduced Toxicity, and Increased...

Area of Science:

• Biomaterials Science
• Nanotechnology
• Cancer Therapeutics

Background:

• Anticancer drug resistance significantly contributes to cancer patient mortality.
• Positively charged anticancer macromolecules exhibit unselective toxicity.
• Biodegradable polymers show promise in overcoming drug resistance.

Purpose of the Study:

• To develop a targeted drug delivery system to overcome anticancer drug resistance.
• To synthesize an anionic biodegradable polycarbonate carrier for complexation with anticancer polymers.
• To evaluate the efficacy and safety of the resulting nanocomplexes for cancer treatment.

Main Methods:

• Synthesis of an anionic biodegradable polycarbonate carrier conjugated with biotin for cancer cell targeting.
• Self-assembly of the anionic carrier with a positively charged anticancer polycarbonate to form nanocomplexes.
• In vitro evaluation of nanocomplexes against drug-susceptible (MCF7) and drug-resistant (MCF7/ADR) breast cancer cells.
• In vivo studies assessing nanocomplex pharmacokinetics, toxicity, and tumor suppression in relevant cancer models.

Main Results:

• Nanocomplexes achieved sizes < 130 nm with high anticancer polymer loading (38-49%).
• Effective inhibition of both drug-susceptible and drug-resistant human breast cancer cell lines with low IC50 values.
• In vivo half-life of the anticancer polymer increased from 1 to 6-8 hours.
• Demonstrated significant tumor growth suppression (32-56%) with reduced systemic toxicity and no observed liver or kidney damage.

Conclusions:

• The developed biotin-targeted nanocomplexes effectively neutralize the toxicity of anticancer polymers.
• These nanocomplexes show potent anticancer activity against resistant cell lines and in vivo tumor models.
• The system offers improved pharmacokinetics, reduced toxicity, and potential for overcoming anticancer drug resistance.