Non-viral gene delivery has been proposed to carry therapeutic genes into mammalian cells with loss of gene functions. In this study, we focus on delivering p53-encoding plasmid DNA into human breast cancer PC3 cell lines, together with paclitaxel to achieve synergistic effects. This cell line has been reported to have loss of p53 function mutation, and as a control study, we provided the same study with human liver carcinoma HepG2 cell lines, which was known to have no such mutation. Cationic amphiphilic oligopeptide, containing Alanine, Phenylalanine, Histidine, and Lysine residues was designed and synthesized in this study to form self-assembled core-shell nanoparticles. By tuning the number of alanine and phenylalanine residues (in the hydrophobic core), we could adjust the CMC to be between 0.05 to 1.1 mg/mL, with the hydrodynamic radius ranging between 100-400 nm. The nanoparticles were able to encapsulate paclitaxel and at the same time bind p53 DNA on the surface of the nanoparticles, without significantly affecting the integrity of the particles. Paclitaxel encapsulation efficiency and loading levels were tested to be around 10.3% and 2.1%, respectively. The particle size of the peptide/DNA complexes were analysed by dynamic light scattering to be around 100-200 nm, while the zeta potential were characterized to be around +20mV. Cell cycle analysis of PC3 cell lines after the treatment with this co-delivery system has shown that synergistic effect could be achieved in arresting cell growth, while that of HepG2 cell lines did not show any synergy. This system may provide a smart strategy to induce cellular senescence in cancer cells with known p53 mutations by harvesting on the synergistic effects of p53 with anti-cancer drugs.