Drug resistance and side effects are the major bottlenecks of current cancer chemotherapy, thus there is an urgent need to search for a molecule or formulation which have anti-cancer property and can overcome multidrug resistance without exhibiting severe side effects. Piperine, an extract from seeds of Piperaceae family plants has anti-metastatic activities and drug resistance reversal effect. However piperine therapeutic applications are limited because of immunotoxicity, reproductive toxicity and poor aqueous solubility. To overcome these associated limitations, piperine encapsulated polyethylene glycol-Polylactide-co-glycolide nanoparticles (P-PEG-PNP) were prepared. P-PEG-PNP were characterized for drug delivery purpose by using zetasizer, electron microscopy, X-ray diffraction and FTIR spectroscopy. Cell viability studies, cell cycle analysis, phosphatidylserine exposure studies and western blotting experiments indicated that P-PEG-PNP kill the MCF-7 cells by apoptotic mechanism. This is the first report that demonstrates the targeted delivery of piperine to MCF-7 cells utilizing P-PEG-PLGA nanoparticles conjugated with aptamer against mucin1. Combination studies of aptamer conjugated P-PEG-PNP and paclitaxel exhibited significant reduction in required paclitaxel dosages for inhibiting the paclitaxel resistant MCF-7 cells growth. In conclusion, targeted delivery of piperine by aptamer conjugated P-PEG-PNP could be used as a safe candidate nanoformulation for adjuvant cancer chemotherapy against drug resistant breast cancers.