Novel anti-tumor strategy: PEG-hydroxycamptothecin conjugate loaded transferrin-PEG-nanoparticles

The aim of the study was to prepare transferrin modified stealth nanoparticles (Tf-PEG-NP) encapsulating poly(ethylene) glycol-hydroxycamptothecin conjugate (PEG-HCPT) and exploit the possiblility of combination of the functions of passive and active targeting by Tf-PEG-NP, as well as sustained drug release in tumor by PEGylated drug for most efficient tumor targeting and anti-tumor effects enhancement. PEG was covalently linked to the 10-hydroxyl group of HCPT to produce PEG-HCPT conjugate. The conjugate was stable, highly water soluable with the cytotoxicity similar to the parent drug. By encapsulation of the drug conjugate in active targeting, long circulating nanoparticles, we further improved its therapeutic efficacy. The prepared Tf-PEG-NP with average diameters of 110nm showed more sustained in vitro release profile. The pharmacokinetic and biodistribution studies found that Tf-PEG-NP demostrated the longest retention time in blood (8.94-fold that of PEG-HCPT), the highest tumor accumulation (9.03-fold, 3.11-fold that of PEG-HCPT and HCPT-loaded counterpart, respectively), as well as the most powerful anti-tumor activity with the inhibition rate up to 93% against S180 tumor in mice (1.85-fold, 1.23-fold that of PEG-HCPT and HCPT-loaded counterpart, respectively). Such Tf-PEG-NP loaded with PEGylated drug conjugates could be one of the promising strategies to deliver anti-tumor drugs to tumor.