Flexible human serum albumin nanocapsules to enhance drug delivery and cellular uptake for photodynamic/chemo cancer therapy

As a non-invasive cancer treatment, photodynamic therapy (PDT) has great applications in superficial tumors because of its high selectivity and low cumulative toxicity. However, the poor tumor-targeting ability and short blood circulation time of conventional photosensitizers (PSs) limit the efficacy of PDT to some extent. In this study, we synthesized flexible hollow human serum albumin (HHSA) and loaded photosensitizer Chlorin e6 (Ce6) and the chemotherapeutic drug Doxorubicin (DOX) for synergistic cancer therapy. HHSA can enhance drug delivery and cellular uptake through targeting gp60 and SPARC receptors and unique flexible hollow structures. The TEM images show that HHSA possesses distinct flexible hollow structures, as well as good monodispersity and deformability. After loading Ce6 and DOX, HHSA@Ce6-DOX displays better therapeutic effects than HHSA@DOX on the growth of 4T1 breast cancers without irradiation. Remarkably, it has a significantly higher therapeutic effect (relative cell activity: 45% vs. 74%) than HHSA@Ce6 under 660 nm irradiation. Furthermore, the excellent biocompatibility of HHSA@Ce6-DOX has been proved both in vitro and in vivo, indicating that it has a promising future in synergistic tumor treatments.