**2.4 Dox release from the complexes**

CPX1 and CPX2 were digested by gelatinase and Dnase I in PBS buffers with different PH values, and the resulted solution was examined by DOX fluorescence quantification.

The digestion abilities of mouse plasma, the supernatant of the tumor homogenate (THS) and liver homogenate (LHS) on CPX1 and CPX2 were also examined. CPX1 and CPX2 solutions were mixed with mouse plasma or the tissue homogenate supernatants for 2 hours. After that, the mixtures were examined by quantification of the DOX fluorescence.

To further confirm the tumor-specific drug-release ability of CPX2, in vivo experiments was performed. Rhodamine labeled PEG-His-alginate (PHA) and FITC-labeled cationic gelatin was used to form CPX2. Hoechst 33258 was used to substitute for DOX because Hoechst 33258 also possess high DNA-affinity like DOX and it show blue fluorescence which could be discriminated from the red fluorescence of PHA and green fluorescence of C-gelatin. PolyAT was used to substitute for polyGC because Hoechst 33258 specifically binds AT in DNA (Jong et al., 1991). This PHA-C-gelatin-polyAT-Hoechst complex was injected into the tumor and liver separately. One hour later, sections of the liver and tumor was examined under microscope.
