| Author |
Wang, Dangge Wang, Tingting Xu, Zhiai Yu, Haijun Feng, Bing Zhang, Junying Guo, Chengyue Yin, Qi Zhang, Zhiwen Li, Yaping |
| Description |
Country affiliation: China Author Affiliation: Wang D ( State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.); Wang T ( State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.); Xu Z ( School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, China.); Yu H ( State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.); Feng B ( State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.); Zhang J ( School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200241, China.); Guo C ( State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.); Yin Q ( State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.); Zhang Z ( State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.); Li Y ( State Key Laboratory of Drug Research and Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.) |
| Abstract |
Conventional chemotherapy shows moderate efficiency against metastatic cancer since it targets only part of the mechanisms regulating tumor growth and metastasis. Here, gold nanorod (GNR)-based host-guest nanoplatforms loaded with docetaxel (DTX) and small interfering RNA (siRNA)-p65 (referred to as DTX-loaded GNR (GDTX)/p65) for chemo-, RNA interference (RNAi), and photothermal ablation (PTA) cooperative treatment of metastatic breast cancer are reported. To prepare the nanoplatform, GNRs are first coated with cyclodextrin (CD)-grafted polyethylenimine (PEI) and then loaded with DTX and siRNA through host-guest interaction with CD and electrostatic interaction with PEI, respectively. Upon near-infrared laser irradiation, GNRs generate a significant hyperthermia effect to trigger siRNA and DTX release. DTX reduces tumor growth by inhibiting mitosis of cancer cells. Meanwhile, siRNA-p65 suppresses lung metastasis and proliferation of cancer cells by blocking the nuclear factor kappa B (NF-κB) pathway and downregulating the downstream genes matrix metalloproteinase-9 (MMP-9) and B cell lymphoma-2 (Bcl-2). It is demonstrated that GDTX/p65 in combination with laser irradiation significantly inhibits the growth and lung metastasis of 4T1 breast tumors. The antitumor results suggest promising potential of the host-guest nanoplatform for combinational treatment of metastatic cancer by using RNAi, chemotherapy, and PTA. |
| Subject Keyword |
Discipline Nanotechnology Breast Neoplasms Pathology Lung Neoplasms Drug Therapy Secondary Mammary Neoplasms, Experimental Nanotubes Chemistry Rna, Small Interfering Metabolism Taxoids Therapeutic Use Animals Antineoplastic Agents Pharmacology Blotting, Western Cell Death Drug Effects Cell Line, Tumor Endocytosis Female Gene Knockdown Techniques Gold Humans Mice Ultrastructure Spectrophotometry, Ultraviolet Static Electricity Temperature Time Factors Journal Article Research Support, Non-u.s. Gov't |
