Alternative and Injectable Preformed Albumin-Bound Anticancer Drug Delivery System for Anticancer and Antimetastasis Treatment

Biomimetic
design has been extensively investigated. The only FDA-approved
biomimetic albumin-bound paclitaxel may not be beneficial to some
treated patients due to rapid dissociation upon intravenous infusion
and no substantial improvement in the drug’s pharmacokinetics
or biodistribution. Herein, we developed an alternative and injectable
preformed albumin-bound anticancer drug delivery. We combined HSA,
Kolliphor HS 15 (HS15), and pirarubicin (THP) via purely physical
forces in a thin-film hydration method to obtain an albumin-bound
complex of HSA-THP. The lack of any chemical reactions preserves HSA
bioactivity, in contrast to the destroyed secondary structure within
AN-THP (albumin nanoparticle of THP) for the harsh manipulation during
preparation. In vitro, HSA-THP showed a significantly higher cellular
uptake efficiency than THP, and the complex was more cytotoxic. In
vivo, HSA-THP showed longer half-life than THP. It also exhibited
greater tumor accumulation and tumor penetration via gp60- and SPARC-mediated
biomimetic transport than THP and AN-THP. As a result, HSA-THP showed
strong antitumor and antimetastasis efficacy, with relatively little
toxicity. These results suggest the clinical potential of biomimetic
tumor-targeted drug delivery.