Triple-negative breast cancer (TNBC) is one of the most invasively malignant human
cancers and its incidence increases year by year. Effective
therapeutics against them needs to be developed urgently. In this study, a kind of
angiopep-2 modified and intelligently particle size-reducible NPs, Angio-DOX-DGL-GNP, was designed for accomplishing both high accumulation and deep penetration within
tumor tissues. On one hand, for improving the cancerous targeting efficiency of NPs,
angiopep-2 was anchored on the surface of NPs to facilitate their accumulation via binding with
low density lipoprotein-receptor related
protein (LRP) overexpressed on TNBC. On the other hand, for achieving high
tumor retention and increasing
tumor penetration, an intelligently particle size-reducible NPs were constructed through fabricating
gelatin NPs (GNP) with
doxorubicin (DOX) loaded dendrigraft poly-
lysine (DGL). In vitro cellular uptake and ex-vivo imaging proved the
tumor targeting effect of Angio-DOX-DGL-GNP. Additionally, the degradation of large-sized Angio-DOX-DGL-GNP by
matrix metalloproteinase-2 (MMP-2) led to the size reduction from 185.7 nm to 55.6 nm. More importantly, the penetration ability of Angio-DOX-DGL-GNP after incubation with MMP-2 was dominantly enhanced in
tumor spheroids. Due to a combinational effect of active targeting and deep
tumor penetration, the
tumor growth inhibition rate of Angio-DOX-DGL-GNP was 74.1% in a 4T1
breast cancer bearing mouse model, which was significantly higher than other groups. Taken together, we successfully demonstrated a promising and effective nanoplatform for TNBC treatment.