Graphical Abstract
View original image
Download original image
Show Outline
Outline
Graphical Abstract
Abstract
Keywords
Electronic Supplementary Material
References
Research Article
Dual pH-responsive "charge-reversal like" gold nanoparticles to enhance tumor retention for chemo-radiotherapy
Zhi Yuan1(
)
)Abstract
The strategy of pH-responsive aggregation in tumor micro-environment (TME) provides an intriguing platform for enhancing tumor retention and exerting therapeutic effects sufficiently. In this work, we have designed an intelligent dual pH-responsive self-aggregating nano gold system (Au@PAH-Pt/DMMA) for the combined chemo-radiotherapy, in which a "charge-reversal like" strategy was utilized to realize irreversible stable aggregation and pH-specific release of cisplatin prodrug in TME. Responsive aggregation increases the cellular uptake of Au@PAH-Pt/DMMA by 55%–60%, and the cellular uptake of Pt after X-ray irradiation can be further enhanced by 80%. Additionally, responsive aggregation greatly slows down the rate of efflux from tumor in vivo. This system not only promotes B16 cell apoptosis as a chemotherapeutic agent (30.4%), it also enhances the effect of chemo-radiotheray (CRT) by promoting apoptosis as a radiosensitizer (55.3%). The colony formation assay results were fitted to cell survival curve of B16 cells and the sensitization enhancement ratio (SER) was calculated to be 1.29, which shows a good radiosensitizing ability. When exposed to X-ray, this nanoplatform reached the ideal therapeutic effect, and the tumor inhibition rate of Au@PAH-Pt/DMMA reached 91.6% with low drug administration frequency and dose of X-ray. Overall, the dual pH-responsive nanoparticles Au@PAH-Pt/DMMA could effectively enhance tumor therapeutic efficiency by combined chemo-radiotherapy, which provides a potential method for clinical transformation of cancer treatment.
Electronic Supplementary Material
Download File(s)
12274_2019_2518_MOESM1_ESM.pdf (3 MB)
References
1
Siegel, R. L.; Miller, K. D.; Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin. 2019, 69, 7-34.
2
Schürmann, R.; Vogel, S.; Ebel, K.; Bald, I. The physico-chemical basis of DNA radiosensitization: Implications for cancer radiation therapy. Chem. —Eur. J. 2018, 24, 10271-10279.
3
Liu, Y.; Chen, W. Q.; Zhang, P. C.; Jin, X. D.; Liu, X. G.; Li, P.; Li, F. F.; Zhang, H. P.; Zou, G. Z.; Li, Q. Dynamically-enhanced retention of gold nanoclusters in HeLa cells following X-rays exposure: A cell cycle phase-dependent targeting approach. Radiother. Oncol. 2016, 119, 544-551.
4
Liu, Y.; Zhang, P. C.; Li, F. F.; Jin, X. D.; Li, J.; Chen, W. Q.; Li, Q. Metal-based NanoEnhancers for future radiotherapy: Radiosensitizing and synergistic effects on tumor cells. Theranostics 2018, 8, 1824-1849.
5
Kim, K.; Oh, K. S.; Park, D. Y.; Lee, J. Y.; Lee, B. S.; Kim, I. S.; Kim, K.; Kwon, I. C.; Kim, S. Y; Yuk, S. H. Doxorubicin/gold-loaded core/shell nanoparticles for combination therapy to treat cancer through the enhanced tumor targeting. J. Control. Release 2016, 228, 141-149.
6
Yi, X.; Chen, L.; Chen, J.; Maiti, D.; Chai, Z. F.; Liu, Z.; Yang, K. Biomimetic copper sulfide for chemo-radiotherapy: Enhanced uptake and reduced efflux of nanoparticles for tumor cells under ionizing radiation. Adv. Funct. Mater. 2018, 28, 1705161.
7
Wang, C. H.; Li, X. H.; Wang, Y.; Liu, Z.; Fu, L.; Hu, L. K. Enhancement of radiation effect and increase of apoptosis in lung cancer cells by thio-glucose-bound gold nanoparticles at megavoltage radiation energies. J. Nanopart. Res. 2013, 15, 1642.
8
Wang, S.; Huang, P.; Chen, X. Y. Hierarchical targeting strategy for enhanced tumor tissue accumulation/retention and cellular internalization. Adv. Mater. 2016, 28, 7340-7364.
9
Fernandes, G. F. D. S.; Fernandes, B. C.; Valente, V.; Dos Santos, J. L. Recent advances in the discovery of small molecules targeting glioblastoma. Eur. J. Med. Chem. 2019, 164, 8-26.
10
Sun, Q. H.; Zhou, Z. X.; Qiu, N. S.; Shen, Y. Q. Rational design of cancer nanomedicine: Nanoproperty integration and synchronization. Adv. Mater. 2017, 29, 1606628.
11
Hu, Q. Y.; Chen, Q.; Gu, Z. Advances in transformable drug delivery systems. Biomaterials 2018, 178, 546-558.
12
Zhang, Y. M.; Huang, F.; Ren, C. H.; Liu, J. J.; Yang, L. J.; Chen, S. Z.; Chang, J. L.; Yang, C. H.; Wang, W. W.; Zhang, C. N. et al. Enhanced radiosensitization by gold nanoparticles with acid-triggered aggregation in cancer radiotherapy. Adv. Sci. 2019, 6, 1801806.
13
Zhang, Y. M.; Chang, J. L.; Huang, F.; Yang, L. J.; Ren, C. H.; Ma, L.; Zhang, W. X.; Dong, H.; Liu, J. J.; Liu, J. F. Acid-triggered in situ aggregation of gold nanoparticles for multimodal tumor imaging and photothermal therapy. ACS Biomater. Sci. Eng. 2019, 5, 1589-1601.
14
Gao, X. H.; Yue, Q.; Liu, Z. N.; Ke, M. J.; Zhou, X. Y.; Li, S. H.; Zhang, J. P.; Zhang, R.; Chen, L.; Mao, Y. et al. Guiding brain-tumor surgery via blood-brain-barrier-permeable gold nanoprobes with acid-triggered MRI/SERRS signals. Adv. Mater. 2017, 29, 1603917.
15
Wang, X. Y.; Chang, Z.; Nie, X.; Li, Y. Y.; Hu, Z. P.; Ma, J. L.; Wang, W.; Song, T.; Zhou, P.; Wang, H. Q. et al. A conveniently synthesized Pt (Ⅳ) conjugated alginate nanoparticle with ligand self-shielded property for targeting treatment of hepatic carcinoma. Nanomed.: Nanotechnol., Biol. Med. 2019, 15, 153-163.
16
Du, J. Z.; Li, H. J.; Wang, J. Tumor-acidity-cleavable maleic acid amide (TACMAA): A powerful tool for designing smart nanoparticles to overcome delivery barriers in cancer nanomedicine. Acc. Chem. Res. 2018, 51, 2848-2856.
17
Kanamala, M.; Wilson, W. R.; Yang, M. M.; Palmer, B. D.; Wu, Z. M. Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review. Biomaterials 2016, 85, 152-167.
18
Yang, S. Y.; Yao, D. F.; Wang, Y. S.; Yang, W. T.; Zhang, B. B.; Wang, D. B. Enzyme-triggered self-assembly of gold nanoparticles for enhanced retention effects and photothermal therapy of prostate cancer. Chem. Commun. 2018, 54, 9841-9844.
19
Ruan, S. B.; Hu, C.; Tang, X.; Cun, X. L.; Xiao, W.; Shi, K. R.; He, Q.; Gao, H. L. Increased gold nanoparticle retention in brain tumors by in situ enzyme-induced aggregation. ACS Nano 2016, 10, 10086-10098.
20
Liu, X. S.; Chen, Y. J.; Li, H.; Huang, N.; Jin, Q.; Ren, K. F.; Ji, J. Enhanced retention and cellular uptake of nanoparticles in tumors by controlling their aggregation behavior. ACS Nano 2013, 7, 6244-6257.
21
Wu, W.; Zhang, Q. J.; Wang, J. T.; Chen, M.; Li, S.; Lin, Z. F.; Li, J. S. Tumor-targeted aggregation of pH-sensitive nanocarriers for enhanced retention and rapid intracellular drug release. Polym. Chem. 2014, 5, 5668-5679.
22
Hainfeld, J. F.; Lin, L.; Slatkin, D. N.; Avraham Dilmanian, F.; Vadas, T. M.; Smilowitz, H. M. Gold nanoparticle hyperthermia reduces radiotherapy dose. Nanomed.: Nanotechnol., Biol. Med. 2014, 10, 1609-1617.
23
Liu, W. J.; Zhang, D.; Li, L. L.; Qiao, Z. Y.; Zhang, J. C.; Zhao, Y. X.; Qi, G. B.; Wan, D.; Pan, J.; Wang, H. In situ construction and characterization of chlorin-based supramolecular aggregates in tumor cells. ACS Appl. Mater. Interfaces 2016, 8, 22875-22883.
24
Cheng, M. B.; Zhang, Y. H.; Zhang, X. L.; Wang, W.; Yuan, Z. One-pot synthesis of acid-induced in situ aggregating theranostic gold nanoparticles with enhanced retention in tumor cells. Biomater. Sci. 2019, 7, 2009-2022.
25
Zhou, Q.; Shao, S. Q.; Wang, J. Q.; Xu, C. H.; Xiang, J. J.; Piao, Y.; Zhou, Z. X.; Yu, Q. S.; Tang, J. B.; Liu, X. R. et al. Enzyme-activatable polymer-drug conjugate augments tumour penetration and treatment efficacy. Nat. Nanotechnol. 2019, 14, 799-809.
26
Pei, M. L.; Jia, X.; Li, G. P.; Liu, P. Versatile polymeric microspheres with tumor microenvironment bioreducible degradation, pH-activated surface charge reversal, pH-triggered "off-on" fluorescence and drug release as theranostic nanoplatforms. Mol. Pharmaceutics 2019, 16, 227-237.
27
Miao, Y. L.; Qiu, Y. D.; Yang, W. J.; Guo, Y. Q.; Hou, H. W.; Liu, Z. Y.; Zhao, X. B. Charge reversible and biodegradable nanocarriers showing dual pH-/reduction-sensitive disintegration for rapid site-specific drug delivery. Colloids Surf. B: Biointerfaces 2018, 169, 313-320.
28
Zhao, X. B.; Wei, Z. H.; Zhao, Z. P.; Miao, Y. L.; Qiu, Y. D.; Yang, W. J.; Jia, X.; Liu, Z. Y.; Hou, H. W. Design and development of graphene oxide nanoparticle/chitosan hybrids showing pH-sensitive surface charge-reversible ability for efficient intracellular doxorubicin delivery. ACS Appl. Mater. Interfaces 2018, 10, 6608-6617.
29
Feng, T.; Ai, X. Z.; An, G. H.; Yang, P. P.; Zhao, Y. L. Charge-convertible carbon dots for imaging-guided drug delivery with enhanced in vivo cancer therapeutic efficiency. ACS Nano 2016, 10, 4410-4420.
30
Du, J. Z.; Sun, T. M.; Song, W. J.; Wu, J.; Wang, J. A tumor-acidity-activated charge-conversional nanogel as an intelligent vehicle for promoted tumoral-cell uptake and drug delivery. Angew. Chem. , Int. Ed. 2010, 49, 3621-3626.
31
Han, K.; Zhang, W. Y.; Zhang, J.; Lei, Q.; Wang, S. B.; Liu, J. W.; Zhang, X. Z.; Han, H. Y. Acidity-triggered tumor-targeted chimeric peptide for enhanced intra-nuclear photodynamic therapy. Adv. Funct. Mater. 2016, 26, 4351-4361.
32
Zhao, C. Y.; Shao, L. H.; Lu, J. Q.; Deng, X. W.; Wu, Y. Tumor acidity-induced sheddable polyethylenimine-poly(trimethylene carbonate)/DNA/polyethylene glycol-2, 3-dimethylmaleicanhydride ternary complex for efficient and safe gene delivery. ACS Appl. Mater. Interfaces 2016, 8, 6400-6410.
33
Yu, B.; Liu, T.; Du, Y. X.; Luo, Z. D.; Zheng, W. J.; Chen, T. F. X-ray-responsive selenium nanoparticles for enhanced cancer chemo-radiotherapy. Colloids Surf. B: Biointerfaces 2016, 139, 180-189.
34
Frens, G. Controlled nucleation for the regulation of the particle size in monodisperse gold suspensions. Nat. Phys. Sci. 1973, 241, 20-22.
35
Zhang, C. W.; Zhao, X. Z.; Guo, S. H.; Lin, T. S.; Guo, H. Q. Highly effective photothermal chemotherapy with pH-responsive polymer-coated drug-loaded melanin-like nanoparticles. Int. J. Nanomedicine 2017, 12, 1827-1840.
36
Kang, S.; Kim, Y.; Song, Y.; Choi, J. U.; Park, E.; Choi, W.; Park, J.; Lee, Y. Comparison of pH-sensitive degradability of maleic acid amide derivatives. Bioorg. Med. Chem. Lett. 2014, 24, 2364-2367.
37
Han, L.; Zhao, J.; Zhang, X.; Cao, W. P.; Hu, X. X.; Zou, G. Z.; Duan, X. L.; Liang, X. J. Enhanced siRNA delivery and silencing gold-chitosan nanosystem with surface charge-reversal polymer assembly and good biocompatibility. ACS Nano 2012, 6, 7340-7351.
38
Bao, Z. R.; He, M. Y.; Quan, H.; Jiang, D. Z.; Zheng, Y.H.; Qin, W. J.; Zhou, Y. F.; Ren, F.; Guo, M. X.; Jiang, C. Z. FePt nanoparticles: A novel nanoprobe for enhanced HeLa cells sensitivity to chemoradiotherapy. RSC Adv. 2016, 6, 35124-35134.
39
Kim, J. A.; Åberg, C.; Salvati, A.; Dawson, K. A. Role of cell cycle on the cellular uptake and dilution of nanoparticles in a cell population. Nat. Nanotechnol. 2012, 7, 62-68.
40
Pucci, M.; Bravatà, V.; Forte, G. I.; Cammarata, F. P.; Messa, C.; Gilardi, M. C.; Minafra, L. Caveolin-1, breast cancer and ionizing radiation. Cancer Genomics Proteomics 2015, 12, 143-152.
41
Franken, N. A. P.; Rodermond, H. M.; Stap, J.; Haveman, J.; Van Bree, C. Clonogenic assay of cells in vitro. Nat. Protoc. 2006, 1, 2315-2319.
42
Werthmöller, N.; Frey, B.; Rückert, M.; Lotter, M.; Fietkau, R.; Gaipl, U. S. Combination of ionising radiation with hyperthermia increases the immunogenic potential of B16-F10 melanoma cells in vitro and in vivo. Int. J. Hyperthermia 2016, 32, 23-30.
43
Sun, M. M.; Peng, D.; Hao, H. J.; Hu, J.; Wang, D. L.; Wang, K.; Liu, J.; Guo, X. M.; Wei, Y.; Gao, W. P. Thermally triggered in situ assembly of gold nanoparticles for cancer multimodal imaging and photothermal therapy. ACS Appl. Mater. Interfaces 2017, 9, 10453-10460.
44
Xing, R. R.; Liu, K.; Jiao, T. F.; Zhang, N.; Ma, K.; Zhang, R. Y.; Zou, Q. L.; Ma, G. H.; Yan, X. H. An injectable self-assembling collagen-gold hybrid hydrogel for combinatorial antitumor photothermal/photodynamic therapy. Adv. Mater. 2016, 28, 3669-3676.
45
Maiti, D.; Chao, Y.; Dong, Z. L.; Yi, X.; He, J. L.; Liu, Z.; Yang, K. Development of a thermosensitive protein conjugated nanogel for enhanced radio-chemotherapy of cancer. Nanoscale 2018, 10, 13976-13985.
46
Goldberg, E. P.; Hadba, A. R.; Almond, B. A.; Marotta, J. S. Intratumoral cancer chemotherapy and immunotherapy: Opportunities for nonsystemic preoperative drug delivery. J. Pharm. Pharmacol. 2002, 54, 159-180.
47
Fakhari, A.; Subramony, J. A. Engineered in-situ depot-forming hydrogels for intratumoral drug delivery. J. Control. Release 2015, 220, 465-475.
48
Liu, Y.; Zhu, Y. Y.; Wei, G.; Lu, W. Y. Effect of carrageenan on poloxamer-based in situ gel for vaginal use: Improved in vitro and in vivo sustained-release properties. Eur. J. Pharm. Sci. 2009, 37, 306-312.
49
Kojarunchitt, T.; Baldursdottir, S.; Dong, Y. D.; Boyd, B. J.; Rades, T.; Hook, S. Modified thermoresponsive Poloxamer 407 and chitosan sol-gels as potential sustained-release vaccine delivery systems. Eur. J. Pharm. Biopharm. 2015, 89, 74-81.
50
Cafaggi, S.; Leardi, R.; Parodi, B.; Caviglioli, G.; Russo, E.; Bignardi, G. Preparation and evaluation of a chitosan salt-poloxamer 407 based matrix for buccal drug delivery. J. Control. Release 2005, 102, 159-169.
51
Thambi, T.; Li, Y.; Lee, D. S. Injectable hydrogels for sustained release of therapeutic agents. J. Control. Release 2017, 267, 57-66.
52
Liu, M.; Ma, S. M.; Liu, M. B.; Hou, Y. F.; Liang, B.; Su, X.; Liu, X. D. Synergistic killing of lung cancer cells by cisplatin and radiation via autophagy and apoptosis. Oncol. Lett. 2014, 7, 1903-1910.
53
Neshastehriz, A.; Khateri, M.; Ghaznavi, H.; Shakeri-Zadeh, A. Investigating the therapeutic effects of alginate nanogel co-loaded with gold nanoparticles and cisplatin on U87-MG human glioblastoma cells. Anticancer Agents Med. Chem. 2018, 18, 882-890.
Pages 2815-2826
Cite this article:
Zhang X, Zhang C, Cheng M, et al. Dual pH-responsive "charge-reversal like" gold nanoparticles to enhance tumor retention for chemo-radiotherapy. Nano Research, 2019, 12(11): 2815-2826. https://doi.org/10.1007/s12274-019-2518-1
Topics:
Metrics & Citations
Article History
Copyright
京公网安备11010802044758号