The limited penetration of nanocarriers into tumors and the slow release of drugs from these carriers to tumor cells are significant challenges in cancer therapy. In this study, we developed a novel drug delivery carrier derived from mesoporous silica, dually modified with the tumor-homing cyclic peptide iRGD (CRGDKGPDC) and the pH-responsive polymer poly(2-ethyl-2-oxazoline) (PEOz) for treating triple-negative breast cancer. The carrier selectively bound to the αvβ3 integrin receptor, which is specifically expressed in MDA-MB-231 breast cancer cells and vessels. Subsequently, it penetrated deep into the tumor parenchyma through NRP-1 receptor-dependent internalization, with the drug-loaded particles releasing drugs rapidly in the acidic cytoplasmic environment. Results indicated that the drug release rate of PEOz-modified formulations was pH-dependent. Lysosomal escape experiments demonstrated that PEOz-modified particles efficiently escaped lysosomes to release drugs. In vitro cytotoxicity assays revealed that iRGD-functionalized particles were more cytotoxic to NRP-1-positive MDA-MB-231 cells compared to NRP-1-negative MCF-7 cells. Cellular uptake studies demonstrated that iRGD mediated enhanced endocytosis of nanoparticles into MDA-MB-231 cells. In vitro tumor cell spheroid penetration assays confirmed that the PEOz and iRGD dual-modified carrier facilitated deeper distribution of DOX in multicellular spheroids compared to free DOX. Moreover, in a nude mouse model of triple-negative breast cancer, the dual-modified drug-loaded carrier significantly inhibited tumor growth without inducing weight loss or liver and kidney damage. This dual-modified mesoporous silica presents a novel and promising delivery carrier for enhancing cancer treatment.