pH-sensitive polymersomes have shown promising potential in drug delivery to cancer cells in past decades. Having various structural characteristics would make them suitable for dual drug delivery applications. In this study, aldehyde-modified PCL and hydrazine-modified PVA were synthesized and were used to form PCL-PVA copolymer through Schiff base reaction mechanism. The obtained structures were characterized by the H-NMR analysis, and it was determined that PCL and PVA are attached by a pH-sensitive hydrazone bond. According to H NMR spectra, PCL-PVA copolymer degree of substitution (DS) was determined 84% and it consists of 38% PVA and 62% PCL as the hydrophile and hydrophobe part, respectively. The solvent switch method was used to synthesize the polymersomes. Drug-free polymersomes which were synthesized with the order of aqueous solvent addition to organic solvent had the lowest size of 136 nm while, the ones synthesized with the order of organic solvent addition to aqueous solvent had the highest loading efficiency for curcumin (92%) and methotrexate (60%). The mean hydrodynamic diameter of drug-loaded polymersomes was obtained 220 nm by DLS and their spherical morphology was confirmed by TEM and SEM. Curcumin and Methotrexate release was evaluated at pH 5.5 and 7.4 and it was demonstrated that the drug release was higher in the acidic environment, confirming the system is pH-sensitive. Also, the cumulative release of CUR and MTX at pH 5.5 after 48 h achieved 91% and 63% respectively. Cytotoxicity assay was also performed and it showed that the dual drug-loaded polymersomes are more toxic than the single drug-loaded carrier and individual free drugs against MCF7 cells. Moreover, no toxicity was shown when the drug-free polymersomes were exposed to MCF7 cells after 48 h. It was also observed that the dual drug-loaded polymersomes were correctly targeted and have high cellular uptake. In general, the results show that this novel pH-sensitive system could be a promising system for breast cancer treatment by approaching co-delivery concept in future investigations.