Smart drug delivery systems based on nanoscale ZnO_Journal of Biomedical Engineering

Authors：

 HUANG Xiao ¹ , CHEN Chun ² , YI Caixia ¹ , ZHENG Xi ¹

1. School of Sports and Health Science, Tongren University, Tongren, Guizhou 554300, P.R.China;
2. College of Material and Chemical Engineering, Tongren University, Tongren, Guizhou 554300, P.R.China;

Corresponding author：

HUANG Xiao, Email: humphrey8531@hotmail.com

Keywords：

drug delivery systems; zinc oxide; smart response; controlled-release; biocompatibility

DOI：

10.7507/1001-5515.201707029

Video：

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In view of the excellent biocompatibility as well as the low cost, nanoscale ZnO shows great potential for drug delivery application. Moreover, The charming character enable nanoscale ZnO some excellent features (e.g. dissolution in acid, ultrasonic permeability, microwave absorbing, hydrophobic/hydrophilic transition). All of that make nanoscale ZnO reasonable choices for smart drug delivery. In the recent decade, more and more studies have focused on controlling the drug release behavior via smart drug delivery systems based on nanoscale ZnO responsive to some certain stimuli. Herein, we review the recent exciting progress on the pH-responsive, ultrasound-responsive, microwave-responsive and UV-responsive nanoscale ZnO-based drug delivery systems. A brief introduction of the drug controlled release behavior and its effect of the drug delivery systems is presented. The biocompatibility of nanoscale ZnO is also discussed. Moreover, its development prospect is looked forward.

Citation： HUANG Xiao, CHEN Chun, YI Caixia, ZHENG Xi. Smart drug delivery systems based on nanoscale ZnO. Journal of Biomedical Engineering, 2018, 35(2): 324-328. doi: 10.7507/1001-5515.201707029 Copy

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2.	Kang T, Li Fangyuan, Baik S, et al. Surface design of magnetic nanoparticles for stimuli-responsive cancer imaging and therapy. Biomaterials, 2017, 136: 98-114.
3.	Darvishi B, Farahmand L, Majidzadeh-A K. Stimuli-responsive mesoporous silica NPs as non-viral dual siRNA/chemotherapy carriers for triple negative breast cancer. Mol Ther Nucleic Acids, 2017, 7: 164-180.
4.	Fouladi F, Steffen K J, Mallik S. Enzyme-responsive liposomes for the delivery of anticancer drugs. Bioconjug Chem, 2017, 28(4): 857-868.
5.	Kanmani P, Rhim J W. Properties and characterization of bionanocomposite films prepared with various biopolymers and ZnO nanoparticles. Carbohydr Polym, 2014, 106: 190-199.
6.	Li Zhen, Li Hongmei, Liu Lixiang, et al. A pH-sensitive nanocarrier for co-delivery of doxorubicin and camptothecin to enhance chemotherapeutic efficacy and overcome multidrug resistance in vitro. RSC Adv, 2015, 5(94): 77097-77105.
7.	Barick K C, Nigam S, Bahadur D. Nanoscale assembly of mesoporous ZnO: A potential drug carrier. J Mater Chem, 2010, 20(31): 6446-6452.
8.	Peng Hongxia, Hu Chuanyue, Hu Jilin, et al. Fe₃O₄@mZnO nanoparticles as magnetic and microwave responsive drug carriers. Micropor Mesopor Mat, 2016, 226: 140-145.
9.	Huang Xiao, Lu Juan, Yue Danyang, et al. Fe₃O₄@ZnO core-shell nanocomposites for efficient and repetitive removal of low density lipoprotein in plasma and on blood vessel. Nanotechnology, 2015, 26(12): 125101.
10.	Tripathy N, Ahmad R, Ko H A, et al. Enhanced anticancer potency using an acid-responsive ZnO-incorporated liposomal drug-delivery system. Nanoscale, 2015, 7(9): 4088-4096.
11.	El-Mekawy R E, Jassas R S. Recent trends in smart and flexible three-dimensional cross-linked polymers: synthesis of chitosan-ZnO nanocomposite hydrogels for insulin drug delivery. MedChemComm, 2017, 8(5): 897-906.
12.	Wang Yinghui, Song Shuyan, Liu Jianhua, et al. ZnO-functionalized upconverting nanotheranostic agent: Multi-modality imaging-guided chemotherapy with on-demand drug release triggered by pH. Angew Chem Int Edit, 2015, 54(2): 536-540.
13.	Dhivya R, Ranjani J, Rajendhran J, et al. pH responsive curcumin/ZnO nanocomposite for drug delivery. Adv Mater Lett, 2015, 6(6): 505-512.
14.	Vimala K, Shanthi K, Sundarraj S, et al. Synergistic effect of chemo-photothermal for breast cancer therapy using folic acid (FA) modified zinc oxide nanosheet. J Colloid Interface Sci, 2017, 488: 92-108.
15.	Cai Xiaoli, Luo Yanan, Yan Hongye, et al. pH-responsive ZnO nanocluster for lung cancer chemotherapy. ACS Appl Mater Interfaces, 2017, 9(7): 5739-5747.
16.	Zeng Ke, Li Jin, Zhang Zhaoguo, et al. Lipid-coated ZnO nanoparticles as lymphatic-targeted drug carriers: study on cell-specific toxicity in vitro and lymphatic targeting in vivo. J Mater Chem B, 2015, 3(26): 5249-5260.
17.	Cai Xiaoli, Luo Yanan, Zhang Weiying, et al. pH-sensitive ZnO quantum dots-doxorubicin nanoparticles for lung cancer targeted drug delivery. ACS Appl Mater Interfaces, 2016, 8(34): 22442-22450.
18.	Zhang Jing, Wu Dan, Li Mengfei, et al. Multifunctional mesoporous silica nanoparticles based on charge-reversal plug-gate nanovalves and acid-decomposable ZnO quantum dots for intracellular drug delivery. ACS Appl Mater Interfaces, 2015, 7(48): 26666-26673.
19.	Ye Daixin, Ma Yingying, Zhao Wei, et al. ZnO-based nanoplatforms for labeling and treatment of mouse tumors without detectable toxic side effects. ACS Nano, 2016, 10(4): 4294-4300.
20.	Huang Xuan, Wu Shanshan, Du Xuezhong. Gated mesoporous carbon nanoparticles as drug delivery system for stimuli-responsive controlled release. Carbon, 2016, 101: 135-142.
21.	Muharnmad F, Guo Mingyi, Qi Wenxiu, et al. pH-triggered controlled drug release from mesoporous silica nanoparticles via intracelluar dissolution of ZnO nanolids. J Am Chem Soc, 2011, 133(23): 8778-8781.
22.	Zhang Haijun, Guo Liting, Ding Shuang, et al. Targeted photo-chemo therapy of malignancy on the chest wall while cardiopulmonary avoidance based on Fe₃O₄@ZnO nanocomposites. Oncotarget, 2016, 7(24): 36602-36613.
23.	Fini M, Tyler W J. Transcranial focused ultrasound: a new tool for non-invasive neuromodulation. Int Rev Psychiat, 2017, 29(2): 168-177.
24.	Shi Ye, Ma Chongbo, Du Yan, et al. Microwave-responsive polymeric core-shell microcarriers for high-efficiency controlled drug release. J Mater Chem B, 2017, 5(19): 3541-3549.
25.	Qiu Hongjin, Cui Bin, Zhao Weiwei, et al. A novel microwave stimulus remote controlled anticancer drug release system based on Fe₃O₄@ZnO@mGd(2)O(3):Eu@P(NIPAm-co-MAA) multifunctional nanocarriers. J Mater Chem B, 2015, 3(34): 6919-6927.
26.	Peng Hongxia, Cui Bin, Li Guangming, et al. A multifunctional β-CD-modified Fe₃O₄@ZnO:Er³⁺,Yb³⁺ nanocarrier for antitumor drug delivery and microwave-triggered drug release. Mater Sci Eng C, 2015, 46: 253-263.
27.	Bagheri A, Arandiyan H, Boyer C, et al. Lanthanide-doped upconversion nanoparticles: emerging intelligent light-activated drug delivery systems. Adv Sci, 2016, 3(7): 1500437.
28.	黄啸, 王文洪, 王梅, 等. 光控释负载吲哚美辛的氧化锌载药微粒的制备与性能. 精细化工, 2017, 34(1): 92-95, 108.
29.	Huang Xiao, Wang Xiaoying, Wang Sichun, et al. UV and dark-triggered repetitive release and encapsulation of benzophenone-3 from biocompatible ZnO nanoparticles potential for skin protection. Nanoscale, 2013, 5(12): 5596-5601.
30.	黄啸, 郑曦, 易彩霞. 光响应多功能药物载体的制备及其对宫颈癌细胞的抑制作用. 材料导报, 2017, 31(10): 37-40.
31.	Huang Xiao, Zheng Xi, Yi Caixia, et al. P(BA-co-HBA) coated Fe₃O₄@ZnO nanoparticles as photo-responsive multifunctional drug delivery systems for safer cancer therapy. Nano, 2016, 11(5): 1650057.
32.	Kong Fei, Huang Xiao, Yue Danyang, et al. A biocompatible and magnetic nanocarrier with a safe UV-initiated docetaxel release and cancer secretion removal properties increases therapeutic potential for skin cancer. Mater Sci Eng C, 2017, 76: 579-585.
33.	Choi S J, Choy J H. Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction. Int J Nanomedicine, 2014, 9(2): 261-269.
34.	Saptarshi S R, Duschl A, Lopata A L. Biological reactivity of zinc oxide nanoparticles with mammalian test systems: an overview. Nanomedicine, 2015, 10(13): 2075-2092.
35.	Ivask A, Juganson K, Bondarenko O, et al. Mechanisms of toxic action of Ag, ZnO and CuO nanoparticles to selected ecotoxicological test organisms and mammalian cells in vitro: A comparative review. Nanotoxicology, 2014, 8(S1): 57-71.
36.	杨霞, 江米足. 纳米氧化锌的毒性作用及机制研究进展. 浙江大学学报:医学版, 2014, 43(2): 218-226,.
37.	Ng C T, Yong L Q, Hande M P, et al. Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster. Int J Nanomedicine, 2017, 2017(12): 1621-1637.
38.	Liu Jing, Zhao Yong, Ge Wei, et al. Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through theγ-H2AX and NF-κB signaling pathways. Oncotarget, 2017, 8(26): 42673-42692.
39.	Shalini D, Senthikumar S, Rajaquru P. Effect of size and shape on toxicity of zinc oxide (ZnO) nanomaterials in human peripheral blood lymphocytes. Toxicol Mech Methods, 2017. DOI: 10.1080/15376516.2017.1366609.
40.	Xiong Huanming. ZnO nanoparticles applied to bioimaging and drug delivery. Adv Mater, 2013, 25(37, SI): 5329-5335.
41.	Chen Tong, Zhao Tong, Wei Dongfeng, et al. Core-shell nanocarriers with ZnO quantum dots-conjugated Au nanoparticle for tumor-targeted drug delivery. Carbohydr Polym, 2013, 92(2): 1124-1132.
42.	Rakhshaei R. Namazi H. A potential bioactive wound dressing based on carboxymethyl cellulose/ZnO impregnated MCM-41 nanocomposite hydrogel. Mater Sci Eng C, 2017, 73: 456-464.

1. Karimi M, Ghasemi A, Zangabad P S, et al. Smart micro/nanoparticles in stimulus-responsive drug/gene delivery systems. Chem Soc Rev, 2016, 45(5): 1457-1501.
2. Kang T, Li Fangyuan, Baik S, et al. Surface design of magnetic nanoparticles for stimuli-responsive cancer imaging and therapy. Biomaterials, 2017, 136: 98-114.
3. Darvishi B, Farahmand L, Majidzadeh-A K. Stimuli-responsive mesoporous silica NPs as non-viral dual siRNA/chemotherapy carriers for triple negative breast cancer. Mol Ther Nucleic Acids, 2017, 7: 164-180.
4. Fouladi F, Steffen K J, Mallik S. Enzyme-responsive liposomes for the delivery of anticancer drugs. Bioconjug Chem, 2017, 28(4): 857-868.
5. Kanmani P, Rhim J W. Properties and characterization of bionanocomposite films prepared with various biopolymers and ZnO nanoparticles. Carbohydr Polym, 2014, 106: 190-199.
6. Li Zhen, Li Hongmei, Liu Lixiang, et al. A pH-sensitive nanocarrier for co-delivery of doxorubicin and camptothecin to enhance chemotherapeutic efficacy and overcome multidrug resistance in vitro. RSC Adv, 2015, 5(94): 77097-77105.
7. Barick K C, Nigam S, Bahadur D. Nanoscale assembly of mesoporous ZnO: A potential drug carrier. J Mater Chem, 2010, 20(31): 6446-6452.
8. Peng Hongxia, Hu Chuanyue, Hu Jilin, et al. Fe₃O₄@mZnO nanoparticles as magnetic and microwave responsive drug carriers. Micropor Mesopor Mat, 2016, 226: 140-145.
9. Huang Xiao, Lu Juan, Yue Danyang, et al. Fe₃O₄@ZnO core-shell nanocomposites for efficient and repetitive removal of low density lipoprotein in plasma and on blood vessel. Nanotechnology, 2015, 26(12): 125101.
10. Tripathy N, Ahmad R, Ko H A, et al. Enhanced anticancer potency using an acid-responsive ZnO-incorporated liposomal drug-delivery system. Nanoscale, 2015, 7(9): 4088-4096.
11. El-Mekawy R E, Jassas R S. Recent trends in smart and flexible three-dimensional cross-linked polymers: synthesis of chitosan-ZnO nanocomposite hydrogels for insulin drug delivery. MedChemComm, 2017, 8(5): 897-906.
12. Wang Yinghui, Song Shuyan, Liu Jianhua, et al. ZnO-functionalized upconverting nanotheranostic agent: Multi-modality imaging-guided chemotherapy with on-demand drug release triggered by pH. Angew Chem Int Edit, 2015, 54(2): 536-540.
13. Dhivya R, Ranjani J, Rajendhran J, et al. pH responsive curcumin/ZnO nanocomposite for drug delivery. Adv Mater Lett, 2015, 6(6): 505-512.
14. Vimala K, Shanthi K, Sundarraj S, et al. Synergistic effect of chemo-photothermal for breast cancer therapy using folic acid (FA) modified zinc oxide nanosheet. J Colloid Interface Sci, 2017, 488: 92-108.
15. Cai Xiaoli, Luo Yanan, Yan Hongye, et al. pH-responsive ZnO nanocluster for lung cancer chemotherapy. ACS Appl Mater Interfaces, 2017, 9(7): 5739-5747.
16. Zeng Ke, Li Jin, Zhang Zhaoguo, et al. Lipid-coated ZnO nanoparticles as lymphatic-targeted drug carriers: study on cell-specific toxicity in vitro and lymphatic targeting in vivo. J Mater Chem B, 2015, 3(26): 5249-5260.
17. Cai Xiaoli, Luo Yanan, Zhang Weiying, et al. pH-sensitive ZnO quantum dots-doxorubicin nanoparticles for lung cancer targeted drug delivery. ACS Appl Mater Interfaces, 2016, 8(34): 22442-22450.
18. Zhang Jing, Wu Dan, Li Mengfei, et al. Multifunctional mesoporous silica nanoparticles based on charge-reversal plug-gate nanovalves and acid-decomposable ZnO quantum dots for intracellular drug delivery. ACS Appl Mater Interfaces, 2015, 7(48): 26666-26673.
19. Ye Daixin, Ma Yingying, Zhao Wei, et al. ZnO-based nanoplatforms for labeling and treatment of mouse tumors without detectable toxic side effects. ACS Nano, 2016, 10(4): 4294-4300.
20. Huang Xuan, Wu Shanshan, Du Xuezhong. Gated mesoporous carbon nanoparticles as drug delivery system for stimuli-responsive controlled release. Carbon, 2016, 101: 135-142.
21. Muharnmad F, Guo Mingyi, Qi Wenxiu, et al. pH-triggered controlled drug release from mesoporous silica nanoparticles via intracelluar dissolution of ZnO nanolids. J Am Chem Soc, 2011, 133(23): 8778-8781.
22. Zhang Haijun, Guo Liting, Ding Shuang, et al. Targeted photo-chemo therapy of malignancy on the chest wall while cardiopulmonary avoidance based on Fe₃O₄@ZnO nanocomposites. Oncotarget, 2016, 7(24): 36602-36613.
23. Fini M, Tyler W J. Transcranial focused ultrasound: a new tool for non-invasive neuromodulation. Int Rev Psychiat, 2017, 29(2): 168-177.
24. Shi Ye, Ma Chongbo, Du Yan, et al. Microwave-responsive polymeric core-shell microcarriers for high-efficiency controlled drug release. J Mater Chem B, 2017, 5(19): 3541-3549.
25. Qiu Hongjin, Cui Bin, Zhao Weiwei, et al. A novel microwave stimulus remote controlled anticancer drug release system based on Fe₃O₄@ZnO@mGd(2)O(3):Eu@P(NIPAm-co-MAA) multifunctional nanocarriers. J Mater Chem B, 2015, 3(34): 6919-6927.
26. Peng Hongxia, Cui Bin, Li Guangming, et al. A multifunctional β-CD-modified Fe₃O₄@ZnO:Er³⁺,Yb³⁺ nanocarrier for antitumor drug delivery and microwave-triggered drug release. Mater Sci Eng C, 2015, 46: 253-263.
27. Bagheri A, Arandiyan H, Boyer C, et al. Lanthanide-doped upconversion nanoparticles: emerging intelligent light-activated drug delivery systems. Adv Sci, 2016, 3(7): 1500437.
28. 黄啸, 王文洪, 王梅, 等. 光控释负载吲哚美辛的氧化锌载药微粒的制备与性能. 精细化工, 2017, 34(1): 92-95, 108.
29. Huang Xiao, Wang Xiaoying, Wang Sichun, et al. UV and dark-triggered repetitive release and encapsulation of benzophenone-3 from biocompatible ZnO nanoparticles potential for skin protection. Nanoscale, 2013, 5(12): 5596-5601.
30. 黄啸, 郑曦, 易彩霞. 光响应多功能药物载体的制备及其对宫颈癌细胞的抑制作用. 材料导报, 2017, 31(10): 37-40.
31. Huang Xiao, Zheng Xi, Yi Caixia, et al. P(BA-co-HBA) coated Fe₃O₄@ZnO nanoparticles as photo-responsive multifunctional drug delivery systems for safer cancer therapy. Nano, 2016, 11(5): 1650057.
32. Kong Fei, Huang Xiao, Yue Danyang, et al. A biocompatible and magnetic nanocarrier with a safe UV-initiated docetaxel release and cancer secretion removal properties increases therapeutic potential for skin cancer. Mater Sci Eng C, 2017, 76: 579-585.
33. Choi S J, Choy J H. Biokinetics of zinc oxide nanoparticles: toxicokinetics, biological fates, and protein interaction. Int J Nanomedicine, 2014, 9(2): 261-269.
34. Saptarshi S R, Duschl A, Lopata A L. Biological reactivity of zinc oxide nanoparticles with mammalian test systems: an overview. Nanomedicine, 2015, 10(13): 2075-2092.
35. Ivask A, Juganson K, Bondarenko O, et al. Mechanisms of toxic action of Ag, ZnO and CuO nanoparticles to selected ecotoxicological test organisms and mammalian cells in vitro: A comparative review. Nanotoxicology, 2014, 8(S1): 57-71.
36. 杨霞, 江米足. 纳米氧化锌的毒性作用及机制研究进展. 浙江大学学报:医学版, 2014, 43(2): 218-226,.
37. Ng C T, Yong L Q, Hande M P, et al. Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster. Int J Nanomedicine, 2017, 2017(12): 1621-1637.
38. Liu Jing, Zhao Yong, Ge Wei, et al. Oocyte exposure to ZnO nanoparticles inhibits early embryonic development through theγ-H2AX and NF-κB signaling pathways. Oncotarget, 2017, 8(26): 42673-42692.
39. Shalini D, Senthikumar S, Rajaquru P. Effect of size and shape on toxicity of zinc oxide (ZnO) nanomaterials in human peripheral blood lymphocytes. Toxicol Mech Methods, 2017. DOI: 10.1080/15376516.2017.1366609.
40. Xiong Huanming. ZnO nanoparticles applied to bioimaging and drug delivery. Adv Mater, 2013, 25(37, SI): 5329-5335.
41. Chen Tong, Zhao Tong, Wei Dongfeng, et al. Core-shell nanocarriers with ZnO quantum dots-conjugated Au nanoparticle for tumor-targeted drug delivery. Carbohydr Polym, 2013, 92(2): 1124-1132.
42. Rakhshaei R. Namazi H. A potential bioactive wound dressing based on carboxymethyl cellulose/ZnO impregnated MCM-41 nanocomposite hydrogel. Mater Sci Eng C, 2017, 73: 456-464.

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