The invention belongs to the field of new auxiliary materials and new dosage forms of pharmaceutical preparations, and relates to a preparation method and application of a co-assembled nano preparation for targeting
glioblastoma. The preparation method comprises the following steps: firstly, synthesizing a
nitroimidazole dimer with
tumor hypoxia-oxidation-reduction triple response, and assembling the
nitroimidazole dimer with AOH1996 and HRO761 to prepare the nano preparation. The
molar ratio of the AOH1996 to the HRO761 to the
nitroimidazole dimer is 1 to 2 to (0.5 to 2). The key
scaffold protein PCNA for
DNA repair is blocked by the PCNA inhibitor AOH1996, and recruitment and anchoring functions of the key
scaffold protein PCNA on repair factors are destroyed, so that the
glioblastoma is induced to enter a mismatch repair defect state. On the basis, a WRN inhibitor HRO761 is further used for promoting large-scale breakage of chromosomes and finally inducing
cell death. The nitroimidazole dimer and the nitroimidazole dimer are jointly assembled into the nano preparation, and accurate
drug release is realized in response to a hypoxia state and oxidation and reduction signals overexpressed in a
tumor microenvironment, so that the heterogeneity of the
tumor microenvironment is overcome.