LAUSR

Graphical abstract Schematic diagram of the self‐delivery of Janus nano‐prodrug CPT‐SS‐GEM nanoparticles. Figure. No Caption available. Abstract A carrier‐free and reduction‐degradable Janus prodrug, termed as CPT‐SS‐GEM, was fabricated by redox‐sensitive disulfide bond linked gemcitabine and camptothecin. This amphiphilic prodrug showed high drug loading capacity, 42.6% of CPT and 32.2% of GEM, respectively. Benefiting from its amphiphilic property, CPT‐SS‐GEM prodrug could self‐assemble into Janus nano‐prodrug in water without aid of any excipient. The morphology of the nano‐prodrug was spherical particle confirmed by TEM. The rapid drug release from the nano‐prodrug proceeded in a reduction‐dependent manner, more than 90% of the native CPT and GEM were released in the mimic microenvironment of tumor cells (pH 6.5 PBS containing 2 mM DTT) within a period of 3 h. The concurrent and ratio‐metric release of CPT and GEM endowed the Janus nano‐prodrug CPT‐SS‐GEM with pronounced in vitro synergistic antiproliferative effect in multiple cancer cell lines when the inhibition rate of cancer cell proliferation exceeded 50%, including A549, NCI‐H460, HCT116, HT‐29, and MCF‐7/ADR. The combination index values showed as followings, 1.04–0.4 (A549), 0.24–0.60 (NCI‐H460), 0.42–0.16 (HCT116), 1.98–0.15 (HT‐29), 0.36–0.19 (MCF‐7/ADR). Taken together, the carrier‐free, redox‐sensitive Janus nano‐prodrug CPT‐SS‐GEM is a promising candidate as synergistic combination of chemotherapeutics.