Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6is) selectively arrest malignant cells in the G1 phase of cell cycle by inhibiting CDK4/6-mediated phosphorylation of retinoblastoma protein. However, CDK4/6i therapy is often ineffective against triple-negative breast cancer (TNBC) due to the high lysosomal content in TNBC cells, which sequesters the drugs and prevents them from reaching their nuclear target. To address this challenge, three pH- and glutathione-responsive poly(amino acid) nanogels composed of methoxy poly(ethylene glycol) of various lengths and poly(L-glutamic acid-co-L-cystine) (mPEG-P(Glu