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Peptide Dendrimer–Doxorubicin Conjugate‐Based Nanoparticles as an Enzyme‐Responsive Drug Delivery System for Cancer Therapy

Peptide dendrimers have shown promise as an attractive platform for drug delivery. In this study, mPEGylated peptide dendrimer–doxorubicin (dendrimer–DOX) conjugate‐based nanoparticle is prepared and characterized as an enzyme‐responsive drug delivery vehicle. The drug DOX is conjugated to the periphery of dendrimer via an enzyme‐responsive tetra‐peptide linker Gly‐Phe‐Leu‐Gly (GFLG). The dendrimer–DOX conjugate can self‐assemble into nanoparticle, which is confirmed by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy studies. At equal dose, mPEGylated dendrimer–DOX conjugate‐based nanoparticle results in significantly high antitumor activity, and induces apoptosis on the 4T1 breast tumor model due to the evidences from tumor growth curves, an immunohistochemical analysis, and a histological assessment. The in vivo toxicity evaluation demonstrates that nanoparticle substantially avoids DOX‐related toxicities and presents good biosafety without obvious side effects to normal organs of both tumor‐bearing and healthy mice as measured by body weight shift, blood routine test, and a histological analysis. Thus, the mPEGylated peptide dendrimer–DOX conjugate‐based nanoparticle may be a potential nanoscale drug delivery vehicle for the breast cancer therapy.