Department of Radiology, the Affiliated Hospital of Medical School, Ningbo University, 247 Renmin Road, Jiangbei District, Ningbo, 315020, Zhejiang, China.
Cixi Institute of Biomedical Engineering, International Cooperation Base of Biomedical Materials Technology and Application, Chinese Academy of Science (CAS) Key Laboratory of Magnetic Materials and Devices & Zhejiang Engineering Research Center for Biomedical Materials, Ningbo Institute of Materials Technology and Engineering, CAS, 1219 ZhongGuan West Road, Ningbo, 315201, China.
J Nanobiotechnology. 2022 Jul 6;20(1):315. doi: 10.1186/s12951-022-01525-3.
Pancreatic ductal adenocarcinoma (PDAC) is among the deadliest malignant tumors with features of matrix barrier caused poor drug permeability, and susceptibility to drug resistance. Herein, a PDAC and its stromal cell dual-targeted photothermal-chemotherapy strategy is explored to loosen the matrix and reverse drug resistance. To achieve this goal, black TiO-Gd nanocomposites were conjugated with insulin like growth factor 1 (IGF1), and loaded with gemcitabine (GEM) to construct bTiO-Gd-IGF1-GEM nanoprobes. 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. 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 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 conclusion, our results reinforce that the prepared nanoprobes are promising to break matrix barrier and overcome drug resistance in PDAC.
胰腺导管腺癌（PDAC）是最致命的恶性肿瘤之一，具有基质屏障的特征，导致药物渗透性差，易产生耐药性。本文探索了一种 PDAC 及其基质细胞双重靶向光热化疗策略，以松解基质并逆转耐药性。为此，将黑 TiO-Gd 纳米复合材料与胰岛素样生长因子 1（IGF1）偶联，并负载吉西他滨（GEM）构建 bTiO-Gd-IGF1-GEM 纳米探针。体外实验结果表明，在 808nm 近红外光照射下，纳米探针对耐药 MIA PaCa-2 细胞的杀伤作用是单独使用 GEM 的 3.3 倍。体内实验表明，协同光热化疗不仅能松解胰腺肿瘤模型的纤维基质，而且能显著抑制肿瘤生长，在 12 天的治疗后几乎完全消除肿瘤。此外，纳米探针的弛豫率是商用造影剂 Magnevist 的 8.2 倍，因此增强了胰腺肿瘤磁共振成像的信号。总之，我们的结果证实，所制备的纳米探针有望打破 PDAC 中的基质屏障并克服耐药性。
