Figure 7. Proposed mechanism of Combo NP mediated alteration to overcome drug resistant in cancer cells.

(A) In drug resistant cancer cells, PARP-1 is activated rapidly and catalyzes the synthesis of PAR surrounding DNA lesions once DNA damage occurs. DNA repair proteins are recruited by PAR for subsequent repairing, which results in cell recovering. This process causes the failure of traditional chemotherapeutic agents (such as DOX) in cancer treatment. (B) As (III), as a PARP-1 inhibitor, displaces Zn²⁺ in the zinc fingers of PARP-1, and disturbs the synthesis of PAR to interfere DNA damage repairing and accumulate DNA fragmentation in cells, which eventually leads to apoptosis.