Self-defensive nano-assemblies from camptothecin-based antitumor drugs

Area of Science:

• Nanomedicine
• Drug Delivery
• Chemical Engineering

Background:

• Camptothecin (CPT) drugs are susceptible to pH-dependent hydrolysis, leading to loss of efficacy.
• The inactive carboxylate form of CPT is generated through lactone ring-opening.
• Self-assembly offers a promising strategy to enhance drug stability and therapeutic potential.

Purpose of the Study:

• To investigate the self-assembly of CPT-based antitumor drugs into stable nanostructures.
• To explore the influence of molecular structure on the self-assembly morphology.
• To assess the stability and bioactivity preservation of self-assembled CPT drugs.

Main Methods:

• Simple preparation of nano-sized self-assemblies by diluting stock solutions of CPT, 10-hydroxycamptothecin, and carboxylic CPT in aqueous media.
• Characterization of self-assembly kinetics, observing formation within 1 minute at low concentrations (1 × 10⁻⁵ M).
• Analysis of self-assembly morphology (helical nano-ribbons, flat nano-ribbons, cylindric nano-rods) based on drug structure.

Main Results:

• CPT, 10-hydroxycamptothecin, and carboxylic CPT self-assembled into distinct nano-architectures.
• Self-assembly occurred rapidly (<1 min) at a low drug concentration (1 × 10⁻⁵ M).
• J-type self-aggregation resulted in stable nano-assemblies that protected drugs from hydrolysis.

Conclusions:

• Self-assembly is an effective strategy to stabilize CPT-based drugs against hydrolysis.
• The resulting nano-assemblies maintain the bioactivity of CPT drugs for potential tumor therapy.
• Tailoring molecular structure allows control over the morphology of self-assembled nanostructures.