Abstract
Approaches to achieve site-specific and targeted delivery that provide an effective solution to reduce adverse, off target side effects are urgently needed for cancer therapy. Here, we utilized a Trojan-horse-like strategy to carry photosensitizer Chlorin e6 conjugated porous silicon multistage nanovectors with tumor homing mesenchymal stem cells for targeted photodynamic therapy and diagnosis. The inherent versatility of multistage nanovectors permitted the conjugation of photosensitizers to enable precise cell death induction (60%) upon photodynamic therapy, while simultaneously retaining the loading capacity to load various payloads, such as antitumor drugs and diagnostic nanoparticles. Furthermore, the mesenchymal stem cells that internalized the multistage nanovectors conserved their proliferation patterns and in vitro affinity to migrate and infiltrate breast cancer cells. In vivo administration of the mesenchymal stem cells carrying photosensitizer-conjugated multistage nanovectors in mice bearing a primary breast tumor confirmed their tropism toward cancer sites exhibiting similar targeting kinetics to control cells. In addition, this approach yielded in a > 70% decrease in local tumor cell viability after in vivo photodynamic therapy. In summary, these results show the proof-of-concept of how photosensitizer conjugated multistage nanovectors transported by stem cells can target tumors and be used for effective site-specific cancer therapy while potentially minimizing potential negative side effects.