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Co-delivery of Autophagy Inhibitor and Gemcitabine Using a pH-Activatable Core-Shell Nanobomb Inhibits Pancreatic Cancer Progression and Metastasis

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To enhance the penetration of drugs that can inhibit metastasis of pancreatic cancer, a pH-responsive drug delivery system was formulated. Gemcitabine (GEM), a first-line chemotherapeutic drug against PDAC, was loaded in 6PA-modified DGL (PDGL) nanoparticles to afford PDGL-GEM. Then PDGL-GEM was co-precipitated with the autophagy inhibitor chloroquine phosphate (CQ) and calcium phosphate to formulate PDGL-GEM@CAP/CQ.

The size and morphology of the resulting “nanobomb” PDGL-GEM@CAP/CQ were characterized, and their uptake into cells, cytotoxicity and ability to inhibit autophagy were analyzed at pH 6.5 and 7.4. The anti-tumor and anti-metastasis effects of the nanobomb were explored on mice carrying Pan 02 pancreatic tumor xenografts or orthotopic tumors. Read more . . . 

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