Microfluidic Precise Construction and Performance Studies of HA-zein@QT Nanodrug Delivery System

doi:10.7503/cjcu20240480

Abstract

Abstract:

Zein shows great potential in anti-cancer drug delivery systems（DDS）. However， the zein-based DDS prepared by the traditional method has its shortcomings， such as single function， uneven particle size， poor batch reproducibility and anti-cancer effect. In this work， the quercetin（chemical drug）-TCPP（photosensitizer） was used as the model drug（QT）. The co-assembly of the carrier and the model drug was accurately controlled by microfluidic technology. And the HA-zein@QT nanodrug delivery system was precisely constructed to achieve the synergistic anti-tumor. Hyaluronic acid（HA） was used to functionalize α-zein to improve the biocompatibility， stability and cell uptake of the carrier. The microfluidic chip with a high mixing efficiency of 99.54% was screened by computer simulation. The average particle size and PDI of the prepared HA-zein@QT were （50.6±1.7） nm and 0.196， respectively. The results of stability experiments suggested that HA-zein@QT showed high stability after co-incubation with deionized water， PBS and 1640 medium. The results of reactive oxygen species and ·OH detection showed that the ¹O₂ and ·OH increased after exposure to near-infrared light. HA-zein@QT showed a low hemolysis rate（3.75%） after co-incubation with red blood cells. And a high survival rate（>84.57%） of non-tumor cells was obtained. This evidence indicated that the prepared DDS had high biocompatibility. The cytotoxicity experiment showed that the survival rates of A549， HCT116 and HCT8 cells were 28.2%， 20.2% and 24.6%， respectively. This indicated that HA-zein@QT had a high inhibitory ability to tumor cells. It is expected that the microfluidics precise construction of zein-based DDS will provide a new strategy for achieving high efficiency and minimal side effects in anti-tumor drug delivery.

Key words: Zein, Microfluidic, Drug delivery, Combination therapy

CLC Number:

O621

TrendMD:

CHEN Minghui, LIU Mohao, LI Yong, CHENG Hang, GENG Peng, QIU Kuncheng, DENG Gaigai, ZENG Jianhong, HUANG Wenquan. Microfluidic Precise Construction and Performance Studies of HA-zein@QT Nanodrug Delivery System[J]. Chem. J. Chinese Universities, 2025, 46(3): 20240480.

Figures/Tables 8

References 27

1	Bray F.， Ferlay J.， Soerjomataram I.， Siegel R. L.， Torre L. A.， Jemal A.， CA⁃Cancer J. Clin.， 2018， 68（6）， 394—424
2	Sao W.， Lee J. Y.， Li F. Y.， Ling D. S.， Chem. J. Chinese Universities， 2020， 4111）， 2356—2382（邵伟， Lee Jiyoung，李方园，凌代舜. 高等学校化学学报， 2020， 41（11）， 2356—2382
3	Zhang S. W.， Wang J.， Kong Z. Q.， Sun X. X.， He Z. G.， Sun B. J.， Luo C.， Sun J.， Biomaterials， 2022， 282， 121433
4	Mao J. J.， Pillai G. G.， Andrade C. J.， Ligibel J. A.， Basu P.， Cohen L.， Khan I. A.， Mustian K. M.， Puthiyedath R.， Dhiman K. S.， Lao L. X.， Ghelman R.， Guido P. C.， Lopez G.， Gallego-Perez D. F.， Salicrup L. A.， CA⁃Cancer J. Clin.， 2022， 72（2）， 144—164
5	Karges J.， Angew. Chem. Int. Ed.， 2022， 61（5）， e202112236
6	Liu X. B.， Ibarra⁃Sanchez L. A.， Miller M. J.， Lee Y. S.， Curr. Res. Food Sci.， 2022， 5， 1110—1117
7	Yu X. L.， Han N.， Dong Z. Y.， Dang Y. N.， Zhang Q.， Hu W. J.， Wang C. H.， Du S. Y.， Lu Y.， ACS Appl. Mater. Interfaces， 2022， 14（38）， 42988—43009
8	Song J. R.， Sun C. X.， Gul K.， Mata A.， Fang Y. P.， Compr. Rev. Food Sci. Food Saf.， 2021， 20（2）， 1120—1149
9	Liu G. J.， An D. Y.， Li J. J.， Deng S. M.， Front. Pharmacol.， 2023， 14， 1120251
10	Wang Y.， Zhang C.， Xiao M.， Ganesan K.， Gao F.， Liu Q. Q.， Ye Z.， Sui Y.， Zhang F.， Wei K. H.， Wu Y. B.， Wu J. M.， Du B.， Xu C.， Li Y.， Li P.， Zhang J. M.， Chen J. P.， J. Drug Deliv. Sci. Tec.， 2023， 79， 103922
11	Zhang X. Y.， Cheng Y. X.， Lin H.， Zhang H. L.， Zhang W. N.， He J. B.， LWT⁃Food Sci. Technol.， 2024， 203， 116376
12	Wang Q.， Gao Z. L.， Zhao K. J.， Zhang P. Y.， Zhong Q. Z.， Yu Q.， Zhai S. M.， Cui J. W.， Chin. Chem. Lett.， 2022， 33（4）， 1917—1922
13	Liu Y.， Yang G. Z.， Hui Y.， Ranaweera S.， Zhao C. X.， Small， 2022， 18（36）， 2106580
14	Ahn J.， Ko J.， Lee S.， Yu J.， Kim Y.， Jeon N. L.， Adv. Drug Deliv. Rev.， 2018， 128， 29—53
15	Gao Z. J.， Mansor M. H.， Winder N.， Demiral S.， Maclnnes J.， Zhao X. B.， Muthana M.， Pharmaceutics， 2023， 15（7）， 1811
16	Fondaj D.， Arduino I.， Lopedota A. A.， Denora N.， Iacobazzi R. M.， Pharmaceutics， 2023， 15（7）， 1953
17	Na G. S.， Joo J. U.， Lee J. Y.， Yun Y.， Kaang B. K.， Yang J. S.， Kim K.， Kim D. P.， J. Control. Release， 2024， 373， 161—171
18	Wang Q. M.， Tang Y. W.， Yang Y. X.， Lei L.， Lei X. J.， Zhao J. C.， Zhang Y. H.， Li L.， Wang Q.， Ming J.， Food Hydrocolloid.， 2022， 124， 107251
19	Shi Y. F.， Rong S.， Guo T. X.， Zhang R. Y.， Xu D. X.， Han Y. H.， Liu F. G.， Su J. Q.， Xu H. X.， Chen S.， Food Chem.， 2024， 430， 137110
20	Li Y. T.， Wan Z. Y.， Zhao S. L.， Lu H.， McClements D. J.， Liu X. B.， Liu F. G.， Food Hydrocolloid.， 2024， 154， 110064
21	Zhu J.， Li F. X.， Wang X. L.， Yu J. Y.， Wu D. Q.， ACS Appl. Mater. Interfaces， 2018， 10（16）， 13304—13316
22	Chen S.， Han Y. H.， Wang Y. Q.， Yang X.， Sun C. X.， Mao L. K.， Gao Y. X.， Food Chem.， 2019， 276， 322—332
23	Liang X.， Cao K. X.， Li W.， Li X. Q.， McClements D. J.， Hu K.， Food Res. Int.， 2021， 145， 110425
24	Chen S.， Han Y. H.， Jian L.， Liao W. Y.， Zhang Y. H.， Gao Y. X.， Carbohyd. Polym.， 2020， 236， 116090
25	Müller V.， Piai J. F.， Fajardo A. R.， Fávaro S. L.， Rubira A. F.， Muniz E. C.， J. Nanomater.， 2011， 2011， 928728
26	Joye I. J.， Davidov⁃Pardo G.， Ludescher R. D.， McClements D. J.， Food Chem.， 2015， 185， 261—267
27	Wang Y. H.， Wan Z. L.， Yang X. Q.， Wang J. M.， Guo J.， Lin Y.， Food Hydrocolloid.， 2016， 54， 40—48

Runs	c（α-zein）/（mg‧mL^‒1）	t/℃	Flow⁃rate ratio/（mL‧min^‒1）	Size/nm	PDI
1	2.5	20	1∶3∶4	354.8±10.6	0.437
2	2.5	30	1∶6∶7	214.3±4.5	0.314
3	2.5	40	1∶9∶10	80.7±1.4	0.247
4	5	30	1∶9∶10	72.5±9.6	0.214
5	5	40	1∶3∶4	293.1±5.0	0.437
6	5	20	1∶6∶7	260.9±29.4	0.389
7	10	40	1∶6∶7	275.2±18.3	0.356
8	10	20	1∶9∶10	53.4±7.8	0.18
9	10	30	1∶3∶4	213.8±16.4	0.416
k1	191.9	231.5	223.0
k2	206.2	162.2	216.3
k3	180.8	185.1	139.5
R	-25.4	-69.3	-83.5
Optimum	5	30	1∶9∶10	50.6±1.7	0.196

Runs	c（α-zein）/（mg‧mL^‒1）	t/℃	Flow⁃rate ratio/（mL‧min^‒1）	Size/nm	PDI
1	2.5	20	1∶3∶4	354.8±10.6	0.437
2	2.5	30	1∶6∶7	214.3±4.5	0.314
3	2.5	40	1∶9∶10	80.7±1.4	0.247
4	5	30	1∶9∶10	72.5±9.6	0.214
5	5	40	1∶3∶4	293.1±5.0	0.437
6	5	20	1∶6∶7	260.9±29.4	0.389
7	10	40	1∶6∶7	275.2±18.3	0.356
8	10	20	1∶9∶10	53.4±7.8	0.18
9	10	30	1∶3∶4	213.8±16.4	0.416
k1	191.9	231.5	223.0
k2	206.2	162.2	216.3
k3	180.8	185.1	139.5
R	-25.4	-69.3	-83.5
Optimum	5	30	1∶9∶10	50.6±1.7	0.196

[1]	ZHANG Dang, SUN Xiaomin, YANG Haiyue, SONG Bohan, CONG Meng, WANG Yuxin, DING Feng, XU Shanshan, BI Sai, WANG Lei. Application of Nanozyme-based Micro/nanomotors in Smart Drug Delivery [J]. Chem. J. Chinese Universities, 2025, 46(1): 20240468.
[2]	SUN Yujie, NIU Zhentian, TONG Haoxuan, HU Yue, YU Bingran, XU Fujian. Ring-opening Preparation of Poly（disulfide）s for Drug Delivery [J]. Chem. J. Chinese Universities, 2025, 46(1): 20240116.
[3]	CHEN Junnian, ZHANG Haifeng, WANG Haibing, YANG Huocheng, LUO Zhong. Research Progress of Precision Antitumor Medicine Based on Supramolecular Drug-delivery Nanosystems [J]. Chem. J. Chinese Universities, 2025, 46(1): 20240267.
[4]	YAN Ziliang, LI Bei, DAI Yunlu. Research Progress in Supramolecular Drug Delivery Nanosystems Based on Polyphenols [J]. Chem. J. Chinese Universities, 2025, 46(1): 20240260.
[5]	CHEN Xiaoping, WANG Xutan, LIU Ning, WANG Qingxiang, NI Jiancong, YANG Weiqiang, LIN Zhenyu. MOFs-based Microfluidic Chips for Real-time Online Determination of Multiple Heavy Metal Ions [J]. Chem. J. Chinese Universities, 2024, 45(2): 20230395.
[6]	FAN Zhirui, FANG Qun, YANG Yi. Single Cell Proteomic Analysis by Mass Spectrometry [J]. Chem. J. Chinese Universities, 2024, 45(11): 20240294.
[7]	GAO Weizhuo, JING Weixuan, DU Yanrui, LI Zehao, HAN Feng, ZHAO Libo, YANG Zhaochu, JIANG Zhuangde. Influence Factors on Induced Potential of Reduced Graphene Oxide-based Microfluidic Voltage Generations [J]. Chem. J. Chinese Universities, 2023, 44(8): 20230033.
[8]	SHENG Jinhan, ZHENG Qizhen, WANG Ming. Non-viral Delivery of CRISPR/Cas9 Genome Editing [J]. Chem. J. Chinese Universities, 2023, 44(3): 20220344.
[9]	WANG Hui, ZHAO Decai, YANG Nailiang, WANG Dan. Gate Keeper in the Smart Hollow Drug Carrier [J]. Chem. J. Chinese Universities, 2023, 44(1): 20220237.
[10]	YANG Jiye, SUN Dayin, WANG Yan, GU Anqi, YE Yilan, DING Shujiang, YANG Zhenzhong. Progresses in Template Synthesis and Applications of Hollow Materials [J]. Chem. J. Chinese Universities, 2023, 44(1): 20220665.
[11]	WU Yushuai, SHANG Yingxu, JIANG Qiao, DING Baoquan. Research Progress of Controllable Self-assembled DNA Origami Structure as Drug Carrier [J]. Chem. J. Chinese Universities, 2022, 43(8): 20220179.
[12]	CHU Binbin, HE Yao. Silicon-based Nanoprobes for Imaging Detection and Therapy of Ocular Diseases [J]. Chem. J. Chinese Universities, 2022, 43(12): 20220546.
[13]	WANG Shiqi, LUO Bowen, YU Jicheng, GU Zhen. Near-infrared-Ⅱ Fluorescence Imaging for Tumor Diagnosis and Therapy [J]. Chem. J. Chinese Universities, 2022, 43(12): 20220577.
[14]	ZHAI Xiaowei, PAN Meidie, SHI Pan, ZHAO Peng, CHEN Dong. One-step High-throughput Controlled Preparation of Biocompatible Water/Water Microcapsules with Triggered Release [J]. Chem. J. Chinese Universities, 2022, 43(12): 20220460.
[15]	WANG Fangyuan, ZHANG Fenxian, LI Yi, GAO Jianhua, NIU Yanbing, SHEN Shaofei. Fabrication of Bionic Leaf Model and Its Application in Agarose Microfluidic Chip [J]. Chem. J. Chinese Universities, 2022, 43(11): 20220445.