Dendrimer–doxorubicin conjugate as enzyme-sensitive and polymeric nanoscale drug delivery vehicle for ovarian cancer therapy

Peptide dendrimer-based nanoparticles have presented significant potential as candidates for drug delivery system. In this study, we synthesized and characterized enzyme-responsive mPEGylated peptide dendrimer–GFLG–doxorubicin conjugate (dendrimer–GFLG–DOX) as a chemotherapeutic drug delivery nano-carrier via a two-step highly efficient copper-catalyzed alkyne–azide click cycloaddition (CuAAC) reaction. The tetra-peptide sequence Gly–Phe–Leu–Gly (GFLG) was explored as an enzyme-responsive linker to connect the doxorubicin (DOX) to the periphery of mPEGylated peptide dendrimer. The dendrimer–GFLG–DOX was capable of self-assembling into nanoparticle, which was proven by dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies. Compared to the free drug DOX, the dendrimer–GFLG–DOX conjugate based nanoparticle demonstrated higher accumulation and retention within SKOV-3 ovarian tumor tissue, resulting in a higher antitumor activity as evidenced from tumor growth curves, tumor growth inhibition analysis, immunohistochemical assessment and in vivo imaging. Moreover, no obvious systemic toxicity was observed via histological assessment. Thus, the mPEGylated peptide dendrimer–DOX conjugate-based nanoparticle may be a promising candidate as a nanoscale and enzyme-sensitive drug delivery vehicle for ovarian cancer therapy.