Autophagy is a lysosome-based evolutionarily conserved process that plays an important role in cellular degradation for the clearance of damaged or superfluous proteins and organelles.Although numerous nanomaterials influence the autophagy process, few examples have been reported to effectively control autophagic flux and ultimately achieve therapeutic potential.Herein, we develop drug/peptide-encapsulated, pH responsive, surface charge-switching poly(β-amino ester) nanoparticles for highly efficient induction of autophagy and interference of breast cancer in vitro and in vivo.Under lysosomal acidic conditions, the pH-sensitive 3-(dibutylamino)-1-propylamine (DBPA) segment would become positively charged, yielding an overall positive zeta potential on the NPs surface, facilitating interactions with the negatively charged lysosome membrane and producing strong autophagy.Finally, high dose of NPs induce lysosomal VATPase complex impairment that damage lysosome, ultimately resulting in autophagic cell death.By encapsulation of gold (Ⅰ) compounds (Au(Ⅰ)) into hydrophobic domains of NPs, the resultant Au(Ⅰ) loaded NPs (Au(Ⅰ)□NPs) showed synergistically induced cancer cell death through regulation autophagy.In addition, we describe the development of autophagy-inducing peptides engineered into polymeric nanoparticles for highly efficient induction of autophagy and treatment of breast cancer in vivo [1].Identification of the pH sensitive nanomaterials for inducing cell death through regulation autophagy may open a new avenue for drug deliver and cancer therapy.