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用于抗肿瘤药物递送的刺激敏感型聚合物载体的研究进展
Research Progress of Stimuli-Sensitive Polymer Carriers for Anti-Tumor Drug Delivery

DOI: 10.12677/JAPC.2019.84008, PP. 65-73

Keywords: 刺激敏感型聚合物纳米载体，pH敏感，氧化还原敏感，低氧敏感，光敏感，超声波敏感，多重刺激响应
Stimulating Sensitive Polymer Nanocarriers, pH Sensitive, Redox Sensitive, Hypoxic Sensitive, Light Sensitive, Ultrasonic Sensitive, Multiple Stimuli Response

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Abstract:

刺激敏感型聚合物纳米载体由于在药物递送和药物的智能控释方面具有良好的应用前景，受到了广大研究人员的广泛关注。其种类包括响应内源刺激的pH敏感聚合物载体、氧化还原敏感聚合物载体和低氧敏感聚合物载体，响应外源刺激的光敏感聚合物载体和超声波敏感聚合物载体。本文主要综述不同刺激敏感型聚合物载体和多重刺激响应聚合物载体的研究进展，激励未来的研究人员设计和合成新型刺激响应聚合物载体，以便实现更加高效的药物递送和智能控释的效果。
Stimuli-sensitive polymer nanocarriers have attracted much attention from researchers because of their good application prospects in drug delivery and intelligent controlled release of drugs. They consist of pH sensitive polymer carriers, redox sensitive polymer carriers, hypoxic sensitive polymeric carriers, light sensitive polymeric carriers and ultrasonically sensitive polymeric carriers. This article reviews the research progress of different stimuli-sensitive polymer carriers and multiple stimuli-responsive polymer carriers, and encourages future researchers to design and synthesize novel stimuli-responsive polymer carriers for more efficient drug delivery and in-telligent controlled release.

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https://doi.org/10.1021/acsnano.6b00870
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[51]  Mao, J., Li, Y., Wu, T., et al. (2016) A Simple Dual-PH Responsive Prodrug-Based Polymeric Micelles for Drug Delivery. ACS Applied Materials & Interfaces, 8, 17109-17117.
https://doi.org/10.1021/acsami.6b04247
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https://doi.org/10.1021/nn9014032
[53]  Shen, Y., Jin, E., Zhang, B., et al. (2010) Prodrugs Forming High Drug Loading Multifunctional Nanocapsules for Intracellular Cancer Drug Delivery. Journal of the American Chemical Society, 132, 4259-4265.
https://doi.org/10.1021/ja909475m
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https://doi.org/10.1038/nmat2569
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https://doi.org/10.1039/C5RA27293A
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[57]  Wu, G., Fang, Y., Yang, S., Lupton, J.R. and Turner, N.D. (2004) Glutathione Metabolism and Its Implications for Health. The Journal of Nutrition, 134, 489-492.
https://doi.org/10.1093/jn/134.3.489
[58]  Aluri, S., Janib, S.M. and Mackay, J.A. (2009) Environmentally Responsive Peptides as Anticancer Drug Carriers. Advnced Drug Delivery Reviews, 61, 940-952.
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https://doi.org/10.1016/j.nano.2017.12.017
[60]  Zhang, Y., Guo, Z., Cao, Z., et al. (2018) Endogenous Albumin-Mediated Delivery of Redox-Responsive Paclitaxel-Loaded Micelles for Targeted Cancer Therapy. Biomaterials, 183, 243-257.
https://doi.org/10.1016/j.biomaterials.2018.06.002
[61]  Sun, C., Li, X., Du, X. and Wang, T. (2018) Redox-Responsive Micelles for Triggered Drug Delivery and Effective Laryngopharyngeal Cancer Therapy. International Journal of Biological Macromolecules, 112, 65-73.
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https://doi.org/10.1021/acsami.7b18245
[63]  Liu, B., Tan, L., He, C., et al. (2018) Redox-Responsive Micelles Self-Assembled from Multi-Block Copolymer for Co-Delivery of Sirna and Hydrophobic Anticancer Drug. Polymer Bulletin, 76, 4237-4257.
https://doi.org/10.1007/s00289-018-2600-y
[64]  Chen, W., Yuan, Y., Cheng, D., et al. (2014) Co-Delivery of Doxorubicin and siRNA with Reduction and pH Dually Sensitive Nanocarrier for Synergistic Cancer Therapy. Small, 10, 2678-2687.
https://doi.org/10.1002/smll.201303951
[65]  Qian, C., Yu, J., Chen, Y., et al. (2016) Light-Activated Hypoxia-Responsive Nanocarriers for Enhanced Anticancer Therapy. Advanced Materials, 28, 3313-3320.
https://doi.org/10.1002/adma.201505869
[66]  Zeng, Y., Ma, J., Zhan, Y., et al. (2018) Hypoxia-Activated Prodrugs and Re-dox-Responsive Nanocarriers. International Journal of Nanomedicine, 13, 6551-6574.
https://doi.org/10.2147/IJN.S173431
[67]  Kizaka-Kondoh, S., Inoue, M., Harada, H. and Hiraoka, M. (2003) Tumor Hypoxia: A Target for Selective Cancer Therapy. Cancer Science, 94, 1021-1028.
https://doi.org/10.1111/j.1349-7006.2003.tb01395.x
[68]  Liu, J.N., Bu, W. and Shi, J. (2017) Chemical Design and Synthesis of Functionalized Probes for Imaging and Treating Tumor Hypoxia. Chemical Reviews, 117, 6160-6224.
https://doi.org/10.1021/acs.chemrev.6b00525
[69]  Thambi, T., Deepagan, V.G., Yoon, H.Y., et al. (2014) Hypoxia-Responsive Polymeric Nanoparticles for Tumor-Targeted Drug Delivery. Biomaterials, 35, 1735-1743.
https://doi.org/10.1016/j.biomaterials.2013.11.022
[70]  Piao, W., Tsuda, S., Tanaka, Y., et al. (2013) Development of Azo-Based Fluorescent Probes to Detect Different Levels of Hypoxia. Angewandte Chemie International Edition, 52, 13028-13032.
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https://doi.org/10.1002/anie.200900255
[72]  Fomina, N., Sankaranarayanan, J. and Almutairi, A. (2012) Photochemical Me-chanisms of Light-Triggered Release from Nanocarriers. Advanced Drug Delivery Reviews, 64, 1005-1020.
https://doi.org/10.1016/j.addr.2012.02.006
[73]  Zhao, Y. (2012) Light-Responsive Block Copolymer Micelles. Macromolecules, 45, 3647-3657.
https://doi.org/10.1021/ma300094t
[74]  Baghbani, F. and Moztarzadeh, F. (2017) Bypassing Multidrug Resistant Ovarian Cancer Using Ultrasound Responsive Doxorubicin/Curcumin Co-Deliver Alginate Nanodroplets. Colloids and Surfaces B: Biointer-faces, 153, 132-140.
https://doi.org/10.1016/j.colsurfb.2017.01.051
[75]  Baghbani, F., Chegeni, M., Moztarzadeh, F., Hadian-Ghazvini, S. and Raz, M. (2017) Novel Ultrasound-Responsive Chitosan/Perfluorohexane Nanodroplets for Image-Guided Smart Delivery of an Anticancer Agent: Curcumin. Materials Science and Engineering: C, 74, 186-193.
https://doi.org/10.1016/j.msec.2016.11.107
[76]  Wang, P., Yin, T., Li, J., et al. (2016) Ultrasound-Responsive Microbubbles for Sonography-Guided siRNA Delivery. Nanomedicine: Na-notechnology, Biology and Medicine, 12, 1139-1149.
https://doi.org/10.1016/j.nano.2015.12.361
[77]  Alex, M.R.A., Nehate, C., Veeranarayanan, S., et al. (2017) Self Assembled Dual Responsive Micelles Stabilized with Protein for Co-Delivery of Drug and siRNA in Cancer Therapy. Biomaterials, 133, 94-106.
https://doi.org/10.1016/j.biomaterials.2017.04.022
[78]  Teo, J.Y., Chin, W., Ke, X., et al. (2017) pH and Redox Dual-Responsive Biodegradable Polymeric Micelles with High Drug Loading for Effective Anticancer Drug Delivery. Nanomedicine: Nanotechnology, Biology and Medicine, 13, 431-442.
https://doi.org/10.1016/j.nano.2016.09.016
[79]  Zhuang, W., Xu, Y., Li, G., et al. (2018) Redox and pH Dual-Responsive Polymeric Micelles with Aggregation-Induced Emission Feature for Cellular Imaging and Chemotherapy. ACS Applied Materials & Interfaces, 10, 18489-18498.
https://doi.org/10.1021/acsami.8b02890
[80]  Yu, H., Cui, Z., Yu, P., et al. (2015) pH-and NIR Light-Responsive Micelles with Hyperthermia-Triggered Tumor Penetration and Cytoplasm Drug Release to Reverse Doxorubicin Resistance in Breast Cancer. Advanced Functional Materials, 25, 2489-2500.
https://doi.org/10.1002/adfm.201404484
[81]  Xu, X., Li, L., Zhou, Z., Sun, W. and Huang, Y. (2016) Dual-pH Responsive Micelle Platform for Co-Delivery of Axitinib and Doxorubicin. International Journal of Pharmaceutics, 507, 50-60.
https://doi.org/10.1016/j.ijpharm.2016.04.060
[82]  Wang, Y., Luo, Q., Zhu, W., et al. (2016) Reduction/pH Dual-Responsive Nano-Prodrug Micelles for Controlled Drug Delivery. Polymer Chemistry, 7, 2665-2673.
https://doi.org/10.1039/C6PY00168H
[83]  Sang, M.M., Liu, F.L., Wang, Y., et al. (2018) A Novel Redox/pH Dual-Responsive and Hyaluronic Acid-Decorated Multifunctional Magnetic Complex Micelle for Targeted Gambogic Acid Delivery for the Treatment of Triple Negative Breast Cancer. Drug Delivery, 25, 1846-1857.
https://doi.org/10.1080/10717544.2018.1486472
[84]  Li, J., Yu, X., Wang, Y., et al. (2014) A Reduction and pH Dual-Sensitive Polymeric Vector for Long-Circulating and Tumor-Targeted Sirna Delivery. Advanced Materials, 26, 8217-8224.
https://doi.org/10.1002/adma.201403877

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