Synthesis of pH-responsive triazine skeleton nano-polymer composite containing AIE group for drug delivery

doi:10.1007/s11706-021-0539-7

Front. Mater. Sci.

2021, Vol. 15

Issue (1) : 113-123 https://doi.org/10.1007/s11706-021-0539-7

RESEARCH ARTICLE

Synthesis of pH-responsive triazine skeleton nano-polymer composite containing AIE group for drug delivery

Yifan ZHANG¹, Xueying PENG¹, Xinbo JING¹, Lin CUI²(

), Shengchao YANG¹, Jianning WU¹, Guihua MENG¹, Zhiyong LIU¹(

), Xuhong GUO^1,³

¹. School of Chemistry and Chemical Engineering, Shihezi University/Key Laboratory of Green Process for Chemical Engineering/ Key Laboratory for Chemical Materials of Xinjiang Uygur Autonomous Region/Engineering Center for Chemical Materials of Xinjiang Bingtuan, Shihezi University, Shihezi 832003, China
². School of Medicine, Shihezi University, Shihezi 832003, China
³. State Key Laboratory of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China

Download: PDF(1540 KB) HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks

Abstract

We exploited a unique porous structure of the nano-covalent triazine polymer (NCTP) containing aggregation-induced emission (AIE) group to achieve controlled release and drug tracking in tumor acidic microenvironment. NCTP was synthesized by the Friedel–Crafts alkylation and the McMurry coupling reaction. It not only had strong doxorubicin (DOX)-loading capacity due to its high specific surface area and large pore volume, but also showed the significant cumulative drug release as a result of the pH response of triazine polymers. NCTP was induced luminescence after mass accumulation near tumor cells. Besides, it had excellent biocompatibility and obvious antineoplastic toxicity. The results demonstrate that NCTP as a utility-type drug carrier provides a new route for designing the multi-functional drug delivery platform.

Keywords triazine skeleton structure pH response aggregation-induced emission drug delivery

Corresponding Author(s): Lin CUI,Zhiyong LIU

Online First Date: 22 January 2021 Issue Date: 11 March 2021

Cite this article:

Yifan ZHANG,Xueying PENG,Xinbo JING, et al. Synthesis of pH-responsive triazine skeleton nano-polymer composite containing AIE group for drug delivery[J]. Front. Mater. Sci., 2021, 15(1): 113-123.

URL:

https://academic.hep.com.cn/foms/EN/10.1007/s11706-021-0539-7
https://academic.hep.com.cn/foms/EN/Y2021/V15/I1/113

Fig.1 Scheme 1 Synthesis of the pH responsive triazine skeleton nano-polymer (NCTP) composite containing the AIE group for drug delivery.

Fig.2 Scheme 2 Processes of AIE and tumor acid microenvironment-triggered drug release.

Fig.3 (a) XRD patterns of NCTP, TPE and CC. (b) FTIR spectrum of NCTP. (c)¹³C NMR spectrum of TPE. (d)¹H NMR spectrum of NCTP.

Fig.4 Morphology analyses of NCTP: (a)(b) TEM images of NCTP particles; (c)(d) size distributions of NCTP and NCTP-DOX micelles in the PBS solution; (e)(f) N₂ adsorption/desorption isotherms for NCTP and NCTP-DOX.

Tab.1 BET data of NCTP and NCTP-DOX

Fig.5 (a) UV–vis absorption spectrum of NCTP in the PBS solution (inset: PL spectrum). PL spectra of NCTP at (b) different f(DMSO) values in DMSO/PBS mixtures (c(NCTP)=1000 μg·mL⁻¹) and (c) different concentrations of NCTP (f(DMSO))=0%. (d) PL spectra of NCTP, DOX and NCTP-DOX.

Fig.6 Stable performance of NCTP and NCTP-DOX: (a) change in diameter sizes of NCTP and NCTP-DOX with time; (b) change in zeta potentials of NCTP in the PBS solutions at pH 7.4 and 5.0 with time; (c) TGA results of NCTP.

Fig.7 (a) Variation of the loading rate of DOX in NCTP with the DOX concentration. (b) Variations of cumulative release rates of DOX in PBS at pH 5.0 and 7.4 (37 °C) with time.

Fig.8 Relative cell viabilities of (a) CaSki cells and (b) HeLa cells treated with DOX, NCTP and NCTP-DOX at various concentrations.

1	S N Weingart, L Zhang, M Sweeney, et al.. Chemotherapy medication errors. Lancet Oncology, 2018, 19(4): e191–e199 https://doi.org/10.1016/S1470-2045(18)30094-9 pmid: 29611527
2	P Liu, R Zhang, M Pei. Design of pH/reduction dual-responsive nanoparticles as drug delivery system for DOX: Modulating controlled release behavior with bimodal drug-loading. Colloids and Surfaces B: Biointerfaces, 2017, 160(27): 455–461 https://doi.org/10.1016/j.colsurfb.2017.09.049 pmid: 28985607
3	W D Tap, A J Wagner, P Schöffski, et al.. Effect of doxorubicin plus olaratumab vs doxorubicin plus placebo on survival in patients with advanced soft tissue sarcomas: The announce randomized clinical trial. JAMA: Journal of the American Medical Association, 2020, 323(13): 1266–1276 https://doi.org/10.1001/jama.2020.1707 pmid: 32259228
4	V Krishnan, A K Rajasekaran. Clinical nanomedicine: a solution to the chemotherapy conundrum in pediatric leukemia therapy. Clinical Pharmacology and Therapeutics, 2014, 95(2): 168–178 https://doi.org/10.1038/clpt.2013.174 pmid: 24013811
5	H Xiong, Z Wang, C Wang, et al.. Transforming complexity to simplicity: protein-like nanotransformer for improving tumor drug delivery programmatically. Nano Letters, 2020, 20(3): 1781–1790 https://doi.org/10.1021/acs.nanolett.9b05008 pmid: 32091222
6	D Peer, J M Karp, S Hong, et al.. Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2007, 2(12): 751–760 https://doi.org/10.1038/nnano.2007.387 pmid: 18654426
7	S Wilhelm, A J Tavares, Q Dai, et al.. Analysis of nanoparticle delivery to tumours. Nature Reviews: Materials, 2016, 1(5): 16014 https://doi.org/10.1038/natrevmats.2016.14
8	Z Chai, D Ran, L Lu, et al.. Ligand-modified cell membrane enables the targeted delivery of drug nanocrystals to glioma. ACS Nano, 2019, 13(5): 5591–5601 https://doi.org/10.1021/acsnano.9b00661 pmid: 31070352
9	B Ding, S Shao, C Yu, et al.. Large-pore mesoporous-silica-coated upconversion nanoparticles as multifunctional immunoadjuvants with ultrahigh photosensitizer and antigen loading efficiency for improved cancer photodynamic immunotherapy. Advanced Materials, 2018, 30(52): 1802479 https://doi.org/10.1002/adma.201802479 pmid: 30387197
10	A L B Seynhaeve, M Amin, D Haemmerich, et al.. Hyperthermia and smart drug delivery systems for solid tumor therapy. Advanced Drug Delivery Reviews, 2020, 32: 89–95 https://doi.org/10.1016/j.addr.2020.02.004 pmid: 32092379
11	C Su, Y Liu, R Li, et al.. Absorption, distribution, metabolism and excretion of the biomaterials used in nanocarrier drug delivery systems. Advanced Drug Delivery Reviews, 2019, 143: 97–114 https://doi.org/10.1016/j.addr.2019.06.008 pmid: 31255595
12	H Wang, D Jiang, D Huang, et al.. Covalent triazine frameworks for carbon dioxide capture. Journal of Materials Chemistry A: Materials for Energy and Sustainability, 2019, 7(40): 22848–22870 https://doi.org/10.1039/C9TA06847C
13	Y Yang, H Niu, L Xu, et al.. Triazine functionalized fully conjugated covalent organic framework for efficient photocatalysis. Applied Catalysis B: Environmental, 2020, 269: 118799 https://doi.org/10.1016/j.apcatb.2020.118799
14	D Ji, T Li, H Fuchs. Patterning and applications of nanoporous structures in organic electronics. Nano Today, 2020, 31: 100843 https://doi.org/10.1016/j.nantod.2020.100843
15	A Rengaraj, P Puthiaraj, Y Haldorai, et al.. Porous covalent triazine polymer as a potential nanocargo for cancer therapy and imaging. ACS Applied Materials & Interfaces, 2016, 8(14): 8947–8955 https://doi.org/10.1021/acsami.6b00284 pmid: 26998679
16	B Lu, L Li, L Wei, et al.. Synthesis and thermo-responsive self-assembly behavior of amphiphilic copolymer β-CD–(PCL–P(MEO2MA-co-PEGMA))21 for the controlled intracellular delivery of doxorubicin. RSC Advances, 2016, 6(56): 50993–51004 doi:10.1039/C6RA08108H
17	L Wei, B Lu, L Li, et al.. One-step synthesis and self-assembly behavior of thermo-responsive star-shaped β-cyclodextrin–(P(MEO2MA-co-PEGMA))21 copolymers. Frontiers of Materials Science, 2017, 11(3): 223–232 https://doi.org/10.1007/s11706-017-0388-6
18	X Peng, L Wei, X Jing, et al.. Stimuli-responsive nano-polymer composite materials based on the triazine skeleton structure used in drug delivery. JOM, 2019, 71(1): 308–314 https://doi.org/10.1007/s11837-018-3214-4
19	L Wei, B Lu, L Cui, et al.Folate-conjugated pH-responsive nanocarrier designed for active tumor targeting and controlled release of doxorubicin. Frontiers of Materials Science, 2017, 11(4): 328–343 doi:10.1007/s11706-017-0401-0
20	B B Lu, L L Wei, G H Meng, et al.. Synthesis of self-assemble pH-responsive cyclodextrin block copolymer for sustained anticancer drug delivery. Chinese Journal of Polymer Science, 2017, 35(8): 924–938 doi:10.1007/s10118-017-1947-0
21	S Murugesan, T Scheibel. Copolymer/clay nanocomposites for biomedical applications. Advanced Functional Materials, 2020, 30(17): 1908101 https://doi.org/10.1002/adfm.201908101
22	G Niu, R Zhang, X Shi, et al.. AIE luminogens as fluorescent bioprobes. Trends in Analytical Chemistry, 2020, 123: 115769 https://doi.org/10.1016/j.trac.2019.115769
23	D Ding, D Mao, K Li, et al.. Precise and long-term tracking of adipose-derived stem cells and their regenerative capacity via superb bright and stable organic nanodots. ACS Nano, 2014, 8(12): 12620–12631 https://doi.org/10.1021/nn505554y pmid: 25427294
24	Y Wang, M Chen, N Alifu, et al.. Aggregation-induced emission luminogen with deep-red emission for through-skull three-photon fluorescence imaging of mouse. ACS Nano, 2017, 11(10): 10452–10461 https://doi.org/10.1021/acsnano.7b05645 pmid: 29016105
25	C Gui, E Zhao, R T K Kwok, et al.. AIE-active theranostic system: selective staining and killing of cancer cells. Chemical Science, 2017, 8(3): 1822–1830 https://doi.org/10.1039/C6SC04947H pmid: 30155198
26	R Zhang, G Niu, Q Lu, et al.. Cancer cell discrimination and dynamic viability monitoring through wash-free bioimaging using AIEgens. Chemical Science, 2020, 11(29): 7676–7684 https://doi.org/10.1039/D0SC01213K
27	P Zhang, Z Zhao, C Li, et al.. Aptamer-decorated self-assembled aggregation-induced emission organic dots for cancer cell targeting and imaging. Analytical Chemistry, 2018, 90(2): 1063–1067 https://doi.org/10.1021/acs.analchem.7b03933 pmid: 29275625
28	H Zhang, Z Zhao, AT Turley, et al.Aggregate science: From structures to properties. Advanced Materials, 2020, 32(36): 2001457 https://doi.org/10.1002/adma.202001457
29	J Zhang, M Liang, X Wang, et al.. Visualizing peroxynitrite fluxes in myocardial cells using a new fluorescent probe reveals the protective effect of estrogen. Chemical Communications, 2019, 55(47): 6719–6722 https://doi.org/10.1039/C9CC02591J pmid: 31119226
30	S Rodríguez-Nuévalos, M Parra, S Ceballos, et al.. A nitric oxide induced “click” reaction to trigger the aggregation induced emission (AIE) phenomena of a tetraphenyl ethylene derivative: A new fluorescent probe for NO. Journal of Photochemistry and Photobiology A: Chemistry, 2020, 388: 112132 https://doi.org/10.1016/j.jphotochem.2019.112132
31	X Chen, H Gao, Y Deng, et al.. Supramolecular aggregation-induced emission nanodots with programmed tumor microenvironment responsiveness for image-guided orthotopic pancreatic cancer therapy. ACS Nano, 2020, 14(4): 5121–5134 https://doi.org/10.1021/acsnano.0c02197 pmid: 32283914
32	Y H Kim, H C Jeong, S H Kim, et al.. High-purity-blue and high-efficiency electroluminescent devices based on anthracene. Advanced Functional Materials, 2005, 15(11): 1799–1805 https://doi.org/10.1002/adfm.200500051
33	R K Konidena, K H Lee, J Y Lee. Two-channel emission controlled by a conjugation valve for the color switching of thermally activated delayed fluorescence emission. Journal of Materials Chemistry C: Materials for Optical and Electronic Devices, 2019, 7(32): 9908–9916 https://doi.org/10.1039/C9TC02618E
34	A Rengaraj, P Puthiaraj, Y Haldorai, et al.. Porous covalent triazine polymer as a potential nanocargo for cancer therapy and imaging. ACS Applied Materials & Interfaces, 2016, 8(14): 8947–8955 https://doi.org/10.1021/acsami.6b00284 pmid: 26998679
35	H J Lee, H G Lee, Y B Kwon, et al.. The role of lactose carrier on the powder behavior and aerodynamic performance of bosentan microparticles for dry powder inhalation. European Journal of Pharmaceutical Sciences, 2018, 117: 279–289 https://doi.org/10.1016/j.ejps.2018.03.004 pmid: 29510172
36	B Guo, M Wu, Q Shi, et al.. All-in-one molecular aggregation-induced emission theranostics: fluorescence image guided and mitochondria targeted chemo- and photodynamic cancer cell ablation. Chemistry of Materials, 2020, 32(11): 4681–4691 https://doi.org/10.1021/acs.chemmater.0c01187
37	S Wang, H Chen, J Liu, et al.. NIR-II light activated photosensitizer with aggregation-induced emission for precise and efficient two-photon photodynamic cancer cell ablation. Advanced Functional Materials, 2020, 30(30): 2002546 https://doi.org/10.1002/adfm.202002546
38	J Mei, N L C Leung, R T K Kwok, et al.. Aggregation-induced emission: together we shine, united we soar! Chemical Reviews, 2015, 115(21): 11718–11940 https://doi.org/10.1021/acs.chemrev.5b00263 pmid: 26492387
39	S Wang, F Hu, Y Pan, et al.. Bright AIEgen-protein hybrid nanocomposite for deep and high-resolution in vivo two-photon brain imaging. Advanced Functional Materials, 2019, 29(29): 1902717 https://doi.org/10.1002/adfm.201902717
40	T D Y Kozai, A S Jaquins-Gerstl, A L Vazquez, et al.. Dexamethasone retrodialysis attenuates microglial response to implanted probes in vivo. Biomaterials, 2016, 87: 157–169 https://doi.org/10.1016/j.biomaterials.2016.02.013 pmid: 26923363
41	L H Liu, W X Qiu, Y H Zhang, et al.. A charge reversible self-delivery chimeric peptide with cell membrane-targeting properties for enhanced photodynamic therapy. Advanced Functional Materials, 2017, 27(25): 1700220 https://doi.org/10.1002/adfm.201700220

[1]	Yimin ZHOU, Qingni XU, Chaohua LI, Yuqi CHEN, Yueli ZHANG, Bo LU. Hollow mesoporous silica nanoparticles as nanocarriers employed in cancer therapy: A review[J]. Front. Mater. Sci., 2020, 14(4): 373-386.
[2]	Amina Ben MIHOUB, Boubakeur SAIDAT, Youssef BAL, Céline FROCHOT, Régis VANDERESSE, Samir ACHERAR. Development of new ionic gelation strategy: Towards the preparation of new monodisperse and stable hyaluronic acid/β-cyclodextrin-grafted chitosan nanoparticles as drug delivery carriers for doxorubicin[J]. Front. Mater. Sci., 2018, 12(1): 83-94.
[3]	Lulu WEI, Beibei LU, Lin CUI, Xueying PENG, Jianning WU, Deqiang LI, Zhiyong LIU, Xuhong GUO. Folate-conjugated pH-responsive nanocarrier designed for active tumor targeting and controlled release of doxorubicin[J]. Front. Mater. Sci., 2017, 11(4): 328-343.
[4]	Lei LIU,Peng LIU. Synthesis strategies for disulfide bond-containing polymer-based drug delivery system for reduction-responsive controlled release[J]. Front. Mater. Sci., 2015, 9(3): 211-226.
[5]	Jing LI,Fang-Kui MA,Qi-Feng DANG,Xing-Guo LIANG,Xi-Guang CHEN. Glucose-conjugated chitosan nanoparticles for targeted drug delivery and their specific interaction with tumor cells[J]. Front. Mater. Sci., 2014, 8(4): 363-372.
[6]	Swamiappan SASIKUMAR. Effect of particle size of calcium phosphate based bioceramic drug delivery carrier on the release kinetics of ciprofloxacin hydrochloride: an invitro study[J]. Front Mater Sci, 2013, 7(3): 261-268.
[7]	Hai WANG, Yu-Liang ZHAO, Guang-Jun NIE. Multifunctional nanoparticle systems for combined chemo- and photothermal cancer therapy[J]. Front Mater Sci, 2013, 7(2): 118-128.

Viewed

Full text

Abstract

Cited

Shared

Discussed