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Rapid metabolism of gemcitabine(GEM) reduces its therapeutic potential. We synthesized mPEGb-PCC-g-GEM-g-DC, which self-assembled into micelles and inhibited tumor growth with high accumulation in the tumor compared to free GEM. We conjugated EGFR targeting GE11-peptide to the polymer and prepared mixed micelles with mPEG-b-PCC-g-GEM-g-DC. These GE11-linked mixed micelles showed significant inhibition of tumor growth in orthotopic pancreatic tumor. We found downregulation of mi R-205 and miR-let7 b in pancreatic cancer tissues and cell lines. Considering miR-205 and miR-let7 b to resensitize GEM-resistant pancreatic cancer, we stably overexpressed these miRNAs in MIA PaCa-2 R cells which resulted in its sensitization to GEM. Combination of mi R-205 and GEM was more effective inreducing cell migration and invasion, CSC proliferation, 3 D spheroids and induction of apoptosis. A significant reduction in orthotopic pancreatic tumor size in mice overexpressing miR-205 after intravenous administration of GEM-conjugated polymeric micelles was achieved. We developed GEM-conjugated copolymers to form complex with miR-205 mimic to co-deliver miR-205 and GEM using mixed micelles decorated with EGFR) targeting antibody, cetuximab for site-specific delivery to the tumor after systemic adnistration.5 Cetuximab-linked mixed micellar polyplex containing miR-205 and GEM showed EGFR mediated enhanced transfection and cellular uptake in EGFR expressing MIA PaCa-2 R cells. In orthotopic pancreatic tumor model, cetuximab-linked mixed micellar polyplex containing miR-205 and GEM treated mice showed enhanced accumulation in the tumor after systemic administration. Our findings suggest that mi R-205 helps in sensitizing GEM-resistant pancreatic cancer cells and act as tumor suppressor. Further, targeted delivery of payloads enhanced the accumulation of drugs to tumor.