A Multifunctional Nanoplatform against Multidrug Resistant Cancer: Merging the Best of Targeted Chemo/Gene/Photothermal Therapy |
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Authors: | Wei Cheng Junpeng Nie Nansha Gao Gan Liu Wei Tao Xiaojun Xiao Lijuan Jiang Zhigang Liu Xiaowei Zeng Lin Mei |
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Affiliation: | 1. Division of Life and Health Sciences, Graduate School at Shenzhen, Tsinghua University, Shenzhen, China;2. College of Optoelectronic Engineering, Shenzhen University, Shenzhen, China;3. School of Pharmaceutical Sciences (Shenzhen), Sun Yat‐sen University, Guangzhou, China;4. Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA;5. Institute of Allergy and Immunology, School of Medicine, Shenzhen University, Shenzhen, China |
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Abstract: | Synergistic therapy that combines chemo‐, gene‐, or photothermal means shows great potential for enhancing the therapeutic effects on cancers. Tumor‐targeted nanoparticles based on a doxorubicin (DOX)‐gated mesoporous silica nanocore (MSN) encapsulated with permeability glycoprotein (P‐gp) small interfering RNA (siRNA) and a polydopamine (PDA) outer layer for DOX loading and folic acid decoration are designed. The multifunctional nanoplatform tactfully integrates chemo‐ (DOX), gene‐ (P‐gp siRNA), and photothermal (PDA layer) substances in one system. In vitro results reveal that DOX release behaviors are both pH‐ and thermal‐responsive and the release of co‐delivered P‐gp siRNA is also pH‐dependent due to the pH‐cleavable DOX gatekeeper on MSN. In addition, due to the near‐infrared light‐responsive PDA outer layer and folic acid conjugation, the nanoparticles exhibit outstanding photothermal activity and selective cell targeting ability. Subsequently, in vitro and in vivo antitumor experiments both demonstrate the enhanced antitumor efficacy of the multifunctional nanoparticles, indicating the significance of synergistic therapy combining chemo‐, gene‐, and photothermal treatments in one system. |
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Keywords: | cancer targeted therapy mesoporous silica multidrug resistance polydopamine synergistic therapy |
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