Second, PDAC cell is usually susceptibility to drug resistance. This dense anatomic structure increases intratumor pressure and decreases blood supply in PDAC, consequently weakens drug delivery capability into tumor. First, PDAC is coated by a “scar”-like matrix barrier, which consists of pancreatic stellate cells, fibroblasts, infiltrating inflammatory cells, and collagen fibers. There are many causes for chemotherapy failure in PDAC, and two factors are primary. Chemotherapy, as a major treatment method for advanced PDAC patients, is commonly unsatisfactory for PDAC, and the effective rate of first line drug gemcitabine (GEM) is less than 20%. Pancreatic ductal adenocarcinoma (PDAC) is a severely malignant tumor, with a poor 5-year survival rate of only 9%, and it is estimated to be the second largest contributor to cancer-related death after lung cancer by 2030. In conclusion, our results reinforce that the prepared nanoprobes are promising to break matrix barrier and overcome drug resistance in PDAC. In addition, relaxation rate of the nanoprobes is 8.2 times than commercial contrast agent Magnevist, therefore boosts the signal of magnetic resonance imaging in pancreatic tumor. In vivo experiments indicate the synergetic photothermal-chemotherapy not only loosens fibrous matrix of pancreatic tumor model, but also dramatically inhibits tumor growth, and almost completely eradicates the tumor after 12 days of treatment. In vitro results show that under 808 nm near-infrared irradiation, killing effect of the nanoprobes on drug-resistant MIA PaCa-2 cell is 3.3 times than that of GEM alone. To achieve this goal, black TiO 2-Gd nanocomposites were conjugated with insulin like growth factor 1 (IGF1), and loaded with gemcitabine (GEM) to construct bTiO 2-Gd-IGF1-GEM nanoprobes. Herein, a PDAC and its stromal cell dual-targeted photothermal-chemotherapy strategy is explored to loosen the matrix and reverse drug resistance. Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignant tumors with features of matrix barrier caused poor drug permeability, and susceptibility to drug resistance.
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