The greater cytotoxicity exerted by tt-Mfn-EV in A549 cells compared with HCC827 cells can be attributed to two factors: (1) the higher expression of TfR in A549, which leads to increased tt-Mfn-EV uptake and consequently higher intracellular CDDP levels that promote DNA damage and cell death; and (2) the more acidic intracellular pH in A549 cells (pH 4.3) compared with HCC827 cells (pH 6.0), which results in faster cleavage of the Pt-ester bond and more rapid CDDP activation, thereby enhancing tumor cell killing. Here, TFRC is linked to neoplasm.