Drug-binding albumins forming stabilized nanoparticles for efficient anticancer therapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Pharmacology

Background:

• Albumin serves as a drug carrier, but natural albumin has limited drug-binding sites, hindering drug loading and therapeutic effectiveness.
• Existing albumin-drug conjugates face challenges in serum stability and targeted delivery, impacting overall efficacy.
• Developing novel albumin-based drug delivery systems is crucial for improving cancer therapy.

Purpose of the Study:

• To engineer bovine serum albumin (BSA) with isothiocyanate conjugates to create enhanced paclitaxel (PTX) nanoparticles.
• To evaluate the drug-loading capacity, stability, and pharmacokinetic profiles of the novel BSA-based nanoparticles.
• To assess the in vivo antitumor efficacy of the modified BSA-PTX nanoparticles in preclinical models.

Main Methods:

• Bovine serum albumin (BSA) was modified with various isothiocyanate conjugates (BSA-ITCs).
• Self-assembly was used to form BSA-ITCs/paclitaxel (PTX) nanoparticles, with phenethyl isothiocyanate (PEITC)-modified BSA (BSA-PEITC35) showing optimal results.
• Molecular modeling was employed to understand PTX binding interactions within the modified BSA structure.
• In vivo studies in mouse tumor models assessed nanoparticle stability, blood circulation, tumor accumulation, and antitumor activity.

Main Results:

• Phenethyl isothiocyanate (PEITC)-modified BSA (BSA-PEITC35) demonstrated superior PTX loading and formed highly stable nanoparticles (BSA-PEITC35/PTX).
• Molecular modeling indicated that PEITC modification significantly reduced PTX binding free energy.
• BSA-PEITC35/PTX nanoparticles exhibited enhanced stability, prolonged circulation, and increased tumor accumulation compared to unmodified BSA/PTX.
• The modified nanoparticles demonstrated superior antitumor activity against subcutaneous tumors in mice compared to BSA/PTX and Abraxane.

Conclusions:

• BSA modification with PEITC isothiocyanate conjugates creates highly stable and effective paclitaxel nanoparticles.
• The engineered nanoparticles offer improved drug delivery, pharmacokinetics, and enhanced antitumor efficacy.
• This approach represents a promising strategy for developing advanced albumin-based nanomedicines for cancer treatment.