天然多糖作为核酸载体的研究

张曼; 牧丹; 张屏; 苏日娜

doi:10.14028/j.cnki.1003-3726.2024.23.163

您当前的位置：

首页 >

文章列表页 >

天然多糖作为核酸载体的研究

综述 | 更新时间：2024-02-06

- 天然多糖作为核酸载体的研究
- Studies on Natural Polysaccharides Used as Nucleic Acid Carriers
- 高分子通报 2024年37卷第3期页码：297-308
- 作者机构：
  
  内蒙古医科大学，呼和浩特 010010
- 作者简介：
  
  *苏日娜，E-mail: surinabo@immu.edu.cn
- 基金信息：
  
  国家自然科学基金(22167019);自治区留学回国人员创新创业项目
- DOI：10.14028/j.cnki.1003-3726.2024.23.163
  中图分类号：
- 纸质出版日期：2024-03-20，
  
  收稿日期：2023-05-10，
  
  录用日期：2023-07-26
- 稿件说明：
扫描看全文
张曼, 牧丹, 张屏, 苏日娜. 天然多糖作为核酸载体的研究. 高分子通报, 2024, 37(3), 297–308

Zhang, M.; Mu, D.; Zhang, P.; Su, R. N. Studies on natural polysaccharides used as nucleic acid carriers. Polym. Bull. (in Chinese), 2024, 37(3), 297–308
张曼, 牧丹, 张屏, 苏日娜. 天然多糖作为核酸载体的研究. 高分子通报, 2024, 37(3), 297–308 DOI： 10.14028/j.cnki.1003-3726.2024.23.163.

Zhang, M.; Mu, D.; Zhang, P.; Su, R. N. Studies on natural polysaccharides used as nucleic acid carriers. Polym. Bull. (in Chinese), 2024, 37(3), 297–308 DOI： 10.14028/j.cnki.1003-3726.2024.23.163.

摘要

基因治疗这种堪称革命性的治疗方法，开拓了治疗癌症的新思路

其最关键性问题是实现核酸药物靶向肿瘤组织并精准治疗。核酸药物直接递送存在核酸酶降解代谢、细胞膜上的负电荷排斥现象以及稳定性差等问题，所以核酸药物需要载体协助，成功的载体递送除能使核酸药物在肿瘤区域大量富集外，还要起到药物控释作用，而天然多糖除无毒、生物相容度高、易修饰的特点外，它本身就具有免疫调节、抗肿瘤、抗炎等多种生物活性。本篇总结了最具代表性的五种多糖的结构特征及在核酸药物递送方面的应用，继而归纳了多糖的常用的纳米级载体形式，为构建天然多糖递送核酸的新型载体并将其应用到免疫抗肿瘤治疗研究中奠定基础。

Abstract

Gene therapy

a revolutionary treatment method

has opened up a new way of thinking in the treatment of cancer. The most critical problem of gene therapy is the realization of nucleic acid drugs targeting tumor tissues and precise treatment. Direct delivery of nucleic acid drugs has the problems of nuclease degradation and metabolism

negative charge rejection on cell membrane and poor stability

so nucleic acid drugs need the assistance of the carrier. Successful carrier delivery can not only enrich nucleic acid drugs in tumor areas

but also play the role of drug controlled release. Natural polysaccharide is non-toxic

biocompatibe

elasy to modify

and has immunomodulatory

anti-tumor

anti-inflammatory and other biological activities. This review summarizes the structural characteristics of the five most representative polysaccharides and their applications in nucleic acid drug delivery

and then describes the common nanoscale carrier forms of polysaccharides

which lays a foundation for the construction of a new nucleic acid delivery system based on natural polysaccharides and its application in immunoantitumor therapy.

关键词

基因治疗核酸药物天然多糖药物载体

Keywords

Gene therapyNucleic acid drugsNatural polysaccharidesDurg delivery system

references

S. Eljack,; S. David,; A. Faggad,; I. Chourpa,; E Allard-Vannier,. Nanoparticles design considerations to co-deliver nucleic acids and anti-cancer drugs for chemoresistance reversal. Int. J. Pharm. X, 2022, 4, 100126.

A. Dinesen,; A. Winther,; A. Wall,; A. Märcher,; J. Palmfeldt,; V. Chudasama,; J. Wengel,; K. V. Gothelf,; J. R. Baker,; K. A Howard,. Albumin biomolecular drug designs stabilized through improved thiol conjugation and a modular locked nucleic acid functionalized assembly. Bioconjug. Chem., 2022, 33(2), 333–342.

M. N. Zhao,; R. J. Wang,; K. M. Yang,; Y. H. Jiang,; Y. C. Peng,; Y. K. Li,; Z. Zhang,; J. X. Ding,; S. J Shi,. Nucleic acid nanoassembly-enhanced RNA therapeutics and diagnosis. Acta Pharm. Sin. B, 2023, 13(3), 916–941.

T. A. Debele,; S. L. Mekuria,; H. C Tsai,. Polysaccharide based nanogels in the drug delivery system: application as the carrier of pharmaceutical agents. Mater. Sci. Eng. C, 2016, 68, 964–981.

L. Zhou,; K. Cheng,; T. Liu,; N. Q. Li,; H. Zhang,; Y He,. Fully bio-based poly(pentamethylene glutaramide) with high molecular weight and less glutaric acid cyclization via direct solid-state polymerization. Eur. Polym. J., 2022, 180, 111618.

龚伟, 杨阳, 金义光, 杜丽娜, 张慧, 梅兴国. 新型药物递送系统研究进展. 中国科学:生命科学, 2011, 41(10), 894–903.

闵莉静. 天然植物多糖修饰的聚阳离子作为基因药物载体的研究. 杭州: 浙江大学, 2017.

M. S. Shang,; H. Jiang,; J. Q. Li,; N. Ji,; M. Li,; L. Dai,; J. He,; Y Qin,. A dual physical crosslinking starch-based hydrogel exhibiting high strength, fatigue resistance, excellent biocompatibility, and biodegradability. Food Chem. X, 2023, 18, 100728.

董凡瑜, 刘刻峰, 刘静, 雷建都. 还原响应型羧甲基纤维素基纳米药物载体的构建及其性能研究. 离子交换与吸附, 2020, 36(1), 12–20.

邓淑豪. 葡聚糖功能化糖原作为药物载体和免疫佐剂的研究. 无锡: 江南大学, 2021.

杨志朋. 透明质酸螯合siRNA的纳米药物用于脑胶质瘤的高效治疗. 开封: 河南大学, 2019.

孙玥. 壳聚糖基miRNA递送体系的制备、表征、生物学评价及其在多房棘球蚴感染研究中的应用. 兰州: 兰州交通大学, 2022.

B. B. Zhao,; L. J. Li,; X. X. Lv,; J. Du,; Z. B. Gu,; Z. F. Li,; L. Cheng,; C. M. Li,; Y Hong,. Progress and prospects of modified starch-based carriers in anticancer drug delivery. J. Control. Release, 2022, 349, 662–678.

李良萍. 共载阿霉素和siRNA的自组装叶酸—生物素—季铵化阳离子淀粉纳米粒的制备及体外协同抗肿瘤研究. 芜湖: 安徽师范大学, 2019.

K. Valachová,; M. A. El Meligy,; L Šoltés,. Hyaluronic acid and chitosan-based electrospun wound dressings: Problems and solutions. Int. J. Biol. Macromol., 2022, 206, 74–91.

T. Zhang,; M. M. Abdelaziz,; S. Cai,; X. M. Yang,; D. J. Aires,; M. L Forrest,. Hyaluronic acid carrier-based photodynamic therapy for head and neck squamous cell carcinoma. Photodiagnosis Photodyn. Ther., 2022, 37, 102706.

X. Y. Mo,; F. L. Wu,; Y. Li,; X. L Cai,. Hyaluronic acid-functionalized halloysite nanotubes for targeted drug delivery to CD44-overexpressing cancer cells. Mater. Today Commun., 2021, 28, 102682.

Q. Chen,; X. R. Li,; Y. Xie,; W. C. Hu,; Z. P. Cheng,; H. Zhong,; H. J Zhu,. Azo modified hyaluronic acid based nanocapsules: CD44 targeted, UV-responsive decomposition and drug release in liver cancer cells. Carbohydr. Polym., 2021, 267, 118152.

H. Jariyal,; H. Thakkar,; A. S. Kumar,; M. Bhattacharyya,; R. P. Shah,; A Srivastava,. Extrinsic hyaluronic acid induction differentially modulates intracellular glutamine metabolism in breast cancer stem cells. Int. J. Biol. Macromol., 2022, 218, 679–689.

N. Platonova,; G. Miquel,; B. Regenfuss,; S. Taouji,; C. Cursiefen,; E. Chevet,; A Bikfalvi,. Evidence for the interaction of fibroblast growth factor-2 with the lymphatic endothelial cell marker LYVE-1. Blood, 2013, 121(7), 1229–1237.

Q. Chen,; J. W. Zheng,; L. Y. Wen,; C. Yang,; L. J Zhang,. A multi-functional-group modified cellulose for enhanced heavy metal cadmium adsorption: performance and quantum chemical mechanism. Chemosphere, 2019, 224, 509–518.

Q. X. Wu,; Y. X. Guan,; S. J Yao,. Sodium cellulose sulfate: A promising biomaterial used for microcarriers’ designing. Front. Chem. Sci. Eng., 2019, 13(1), 46–58.

M. P. Tedesco,; V. A. dos Santos Garcia,; J. G. Borges,; D. Osiro,; F. M. Vanin,; C. M. Pedroso Yoshida,; R. A de Carvalho,. Production of oral films based on pre-gelatinized starch, CMC and HPMC for delivery of bioactive compounds extract from acerola industrial waste. Ind. Crops Prod., 2021, 170, 113684.

A. Everaert,; Y. Wouters,; E. Melsbach,; N. Zakaria,; A. Ludwig,; F. Kiekens,; W Weyenberg,. Optimisation of HPMC ophthalmic inserts with sustained release properties as a carrier for thermolabile therapeutics. Int. J. Pharm., 2017, 528(1-2), 395–405.

J. Y. Zhang,; P. Wang,; C. Tan,; Y. S. Zhao,; Y. Zhu,; J. Bai,; X. Xiao,; L. L. Zhang,; D. H. Teng,; J. Tian,; L. C. Liu,; H. B Zhang,. Effects of L.plantarum dy-1 fermentation time on the characteristic structure and antioxidant activity of barley β-glucan in vitro. Curr. Res. Food Sci., 2022, 5, 125–130.

Y. Li,; Y. H. Fan,; H. O. Pan,; H. F. Qian,; X. G. Qi,; G. C. Wu,; H. Zhang,; M. J. Xu,; Z. M. Rao,; L. Wang,; H Ying,. Effects of functional β-glucan on proliferation, differentiation, metabolism and its anti-fibrosis properties in muscle cells. Int. J. Biol. Macromol., 2018, 117, 287–293.

R Mehvar,. Dextrans for targeted and sustained delivery of therapeutic and imaging agents. J. Control. Release, 2000, 69(1), 1–25.

P. P. Sharma,; S. Bhardwaj,; A. Sethi,; V. K. Goel,; M. Grishina,; B Rathi,. Chitosan based architectures as biomedical carriers. Carbohydr. Res., 2022, 522, 108703.

G. Q. Wang,; R. L. Li,; B. Parseh,; G Du,. Prospects and challenges of anticancer agents’ delivery via chitosan-based drug carriers to combat breast cancer: a review. Carbohydr. Polym., 2021, 268, 118192.

F. H. Luo,; Z. X. Fan,; W. Yin,; L. Yang,; T. T. Li,; L. B. Zhong,; Y. Li,; S. Y. Wang,; J. H. Yan,; Z. Q. Hou,; Q. Q Zhang,. pH-Responsive stearic acid-O-carboxymethyl chitosan assemblies as carriers delivering small molecular drug for chemotherapy. Mater. Sci. Eng. C, 2019, 105, 110107.

J. Venkatesan,; J. Y. Lee,; D. S. Kang,; S. Anil,; S. K. Kim,; M. S. Shim,; D. G Kim,. Antimicrobial and anticancer activities of porous chitosan-alginate biosynthesized silver nanoparticles. Int. J. Biol. Macromol., 2017, 98, 515–525.

Y. Maeda,; Y Kimura,. Antitumor effects of various low-molecular-weight chitosans are due to increased natural killer activity of intestinal intraepithelial lymphocytes in sarcoma 180–bearing mice. J. Nutr., 2004, 134(4), 945–950.

T. Torzsas,; C. Kendall.,; M. Sugano.,; Y. Iwamoto.,; A. Rao.,;The influence of high and low molecular weight chitosan on colonic cell proliferation and aberrant crypt foci development in CF1 mice. Food. Chem. Toxicol., 1996, 34(1), 73–77.

杨艺, 赵媛, 孙纪录, 邵娟娟. 化学修饰多糖的方法及生物活性研究进展. 食品工业科技, 2023, 44(11): 468–479.

余越. 基于硫酸化修饰的青钱柳多糖免疫调节活性及分子机制. 南昌: 南昌大学, 2022.

巩晓佩, 张建, 郭筱兵, 毛晓英, 张连富. 硫酸化修饰对红枣多糖结构及抗氧化活性的影响. 食品与机械, 2022, 38(4): 29–34.

李宇涵. 多糖的氧化改性及在生物医药领域的应用. 化学工程与装备, 2022(12), 208–209.

苗兰宁, 贺奕森, 唐涛, 周玉岩, 赵山山. 羧甲基化沙棘多糖钙螯合物稳定性的探究, 中国食品工业, 2023, 365(03), 95–97.

张银英, 朱静祎, 潘裕添, 林志超, 吴启赐. 灵芝多糖羧甲基化修饰及抗氧化性研究. 闽南师范大学学报(自然科学版), 2022, 35(1), 100–108.

M. Thanou,; B. I. Florea,; M. Geldof,; H. E. Junginger,; G Borchard,. Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines. Biomaterials, 2002, 23(1), 153–159.

E. Faizuloev,; A. Marova,; A. Nikonova,; I. Volkova,; M. Gorshkova,; V Izumrudov,. Water-soluble N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan chlo-ride as a nucleic acids vector for cell transfection. Carbohydr. Polym., 2012, 89(4), 1088–1094.

陈桐. 金纳米—两亲性嵌段共聚物靶向药物载体的制备与评价. 兰州: 兰州大学, 2012.

张子木, 黄秀芳, 张琴, 李美东, 张驰, 罗凯. 壶瓶碎米荠多糖硫酸化结构修饰及抗氧化活性研究. 中国粮油学报, 2021, 36(12), 28–33.

Q. X. Wu,; D. Q. Lin,; S. J Yao,. Design of chitosan and its water soluble derivatives-based drug carriers with polyelectrolyte complexes. Mar. Drugs, 2014, 12(12), 6236–6253.

X. Y. He,; S. Y. Wang,; B. Liu,; D. Jiang,; F. Chen,; G. X. Mao,; W. H. Jin,; H. Y. Pan,; W. H Zhong,. Sulfated modification of hyaluronan tetrasaccharide enhances its antitumor activity on human lung adenocarcinoma A549 cells in vitro and in vivo. Bioorg. Med. Chem. Lett., 2022, 75, 128945.

Z. J. Wang,; J. H. Xie,; M. Y. Shen,; S. P. Nie,; M. Y Xie,. Sulfated modification of polysaccharides: synthesis, characterization and bioactivities. Trends Food Sci. Technol., 2018, 74, 147–157.

段冰潮. 基于香菇多糖/聚脱氧核苷酸复合物构建基因/药物载体及其应用研究. 武汉: 武汉大学, 2019.

Y. T. Geng,; H. Xue,; Z. H. Zhang,; A. C. Panayi,; S. Knoedler,; W. Zhou,; B. B. Mi,; G. H Liu,. Recent advances in carboxymethyl chitosan-based materials for biomedical applications. Carbohydr. Polym., 2023, 305, 120555.

R. Hafezi Moghaddam,; S. Dadfarnia,; A. M. H. Shabani,; R. Amraei,; Z Hafezi Moghaddam,. Doxycycline drug delivery using hydrogels of O-carboxymethyl chitosan conjugated with caffeic acid and its composite with polyacrylamide synthesized by electron beam irradiation. Int. J. Biol. Macromol., 2020, 154, 962–973.

P. P. Song,; B. J. Wang,; Q. Pan,; T. Z. Jiang,; X. Y. Chen,; M. Zhang,; J. J. Tao,; X Zhao,. GE11-modified carboxymethyl chitosan micelles to deliver DOX·PD-L1 siRNA complex for combination of ICD and immune escape inhibition against tumor. Carbohydr. Polym., 2023, 312, 120837.

B. E. Benediktsdóttir,; T. Gudjónsson,; Ó. Baldursson,; M Másson,. N-alkylation of highly quaternized chitosan derivatives affects the paracellular permeation enhancement in bronchial epithelia in vitro. Eur. J. Pharm. Biopharm., 2014, 86(1), 55–63.

P. Gonil,; W. Sajomsang,; U. R. Ruktanonchai,; N. Pimpha,; I. Sramala,; O. Nuchuchua,; S. Saesoo,; S. Chaleawlert-umpon,; S Puttipipatkhachorn,. Novel quaternized chitosan containing β-cyclodextrin moiety: synthesis, characterization and antimicrobial activity. Carbohydr. Polym., 2011, 83(2), 905–913.

P. Chatterjee,; S Kumar,. Current developments in nanotechnology for cancer treatment. Mater. Today, 2022, 48, 1754–1758.

方星辰, 牛俊博, 汲晨锋. 基于天然多糖构建纳米药物递送系统的研究进展. 中国药学杂志, 2022, 57(17), 1406–1412.

W. N. Ke,; R. M. Crist,; J. D. Clogston,; S. T. Stern,; M. A. Dobrovolskaia,; P. Grodzinski,; M. A Jensen,. Trends and patterns in cancer nanotechnology research: a survey of NCI’s caNanoLab and nanotechnology characterization laboratory. Adv. Drug Deliv. Rev., 2022, 191, 114591.

K. Peuler,; N. Dimmitt,; C. C Lin,. Clickable modular polysaccharide nanoparticles for selective cell-targeting. Carbohydr. Polym., 2020, 234, 115901.

Y. Zhang,; Z. Cui,; H. Mei,; J. Y. Xu,; T. Zhou,; F. Cheng,; K. P Wang,. Angelica sinensis polysaccharide nanoparticles as a targeted drug delivery system for enhanced therapy of liver cancer. Carbohydr. Polym., 2019, 219, 143–154.

K. Divya,; M. S Jisha,. Chitosan nanoparticles preparation and applications. Environ. Chem. Lett., 2018, 16(1), 101–112.

X. W. Deng,; M. J. Cao,; J. K. Zhang,; K. L. Hu,; Z. X. Yin,; Z. X. Zhou,; X. Q. Xiao,; Y. S. Yang,; W. Sheng,; Y. Wu,; Y Zeng,. Hyaluronic acid-chitosan nanoparticles for co-delivery of MiR-34a and doxorubicin in therapy against triple negative breast cancer. Biomaterials, 2014, 35(14), 4333–4344.

W. E. Rudzinski,; A. Palacios,; A. Ahmed,; M. A. Lane,; T. M Aminabhavi,. Targeted delivery of small interfering RNA to colon cancer cells using chitosan and PEGylated chitosan nanoparticles. Carbohydr. Polym., 2016, 147, 323–332.

A. J. Qiu,; Y. Y. Wang,; G. L. Zhang,; H. B Wang,. Natural polysaccharide-based nanodrug delivery systems for treatment of diabetes. Polymers, 2022, 14(15), 3217.

C. Naveen,; N Shastri,. Polysaccharide Nanomicelles as Drug Carriers. Woodhead Publishing. 2019, 339–363.

J. A. Sun,; L. Y. Han,; S. B Zhang,. Hyaluronic acid prodrug micelles for tumour therapy. J. Drug Target., 2022, 30(1), 22–30.

Y. Shen,; B. H. Wang,; Y. Lu,; A. Ouahab,; Q. Li,; J. S Tu,. A novel tumor-targeted delivery system with hydrophobized hyaluronic acid-spermine conjugates (HHSCs) for efficient receptor-mediated siRNA delivery. Int. J. Pharm., 2011, 414(1-2), 233–243.

K. Y. Choi,; G. Saravanakumar,; J. H. Park,; K Park,. Hyaluronic acid-based nanocarriers for intracellular targeting: interfacial interactions with proteins in cancer. Colloids Surf. B, 2012, 99, 82–94.

I. N. Ahmed,; R. Chang,; W. B Tsai,. Poly(acrylic acid) nanogel as a substrate for cellulase immobilization for hydrolysis of cellulose. Colloids Surf. B, 2017, 152, 339–343.

B. Stawicki,; T. Schacher,; H Cho,. Nanogels as a versatile drug delivery system for brain cancer. Gels, 2021, 7(2), 63.

E. Dalir Abdolahinia,; G. Barati,; Z. Ranjbar-Navazi,; J. Kadkhoda,; M. Islami,; N. Hashemzadeh,; S. Maleki Dizaj,; S Sharifi,. Application of nanogels as drug delivery systems in multicellular spheroid tumor model. J. Drug Deliv. Sci. Technol., 2022, 68, 103109.

Z. Wang,; X. H. Li,; X. J. Zhang,; R. L. Sheng,; Q. Lin,; W. L. Song,; L. Y Hao,. Novel contact lenses embedded with drug-loaded zwitterionic nanogels for extended ophthalmic drug delivery. Nanomaterials, 2021, 11(9), 2328.

G. L. Huang,; H. L Huang,. Application of hyaluronic acid as carriers in drug delivery. Drug Deliv., 2018, 25(1), 766–772.

M. F. Hsu,; Y. S. Tyan,; Y. C. Chien,; M. W Lee,. Hyaluronic acid-based nano-sized drug carrier-containing Gellan gum microspheres as potential multifunctional embolic agent. Sci. Rep., 2018, 8(1), 731.

T. Athamneh,; A. Amin,; E. Benke,; R. Ambrus,; C. S. Leopold,; P. Gurikov,; I Smirnova,. Alginate and hybrid alginate-hyaluronic acid aerogel microspheres as potential carrier for pulmonary drug delivery. J. Supercrit. Fluids, 2019, 150, 49–55.

H. Lee,; H. Mok,; S. Lee,; Y. K. Oh,; T. G Park,. Target-specific intracellular delivery of siRNA using degradable hyaluronic acid nanogels. J. Control. Release, 2007, 119(2), 245–252.

廉晓芯, 刘昕, 赵强, 王波, 许凤, 张学铭. 纤维素衍生物及纳米晶自组装制备功能材料的研究进展. 中国造纸, 2021, 40(5), 77–87.

A. Kumar,; S. W. Zhang,; G. B. Wu,; C. C. Wu,; J. P. Chen,; R. Baskaran,; Z. D Liu,. Cellulose binding domain assisted immobilization of lipase (GSlip-CBD) onto cellulosic nanogel: characterization and application in organic medium. Colloids Surf. B, 2015, 136, 1042–1050.

K. K. Zhu,; T. Ye,; J. J. Liu,; Z. Peng,; S. S. Xu,; J. Q. Lei,; H. B. Deng,; B Li,. Nanogels fabricated by lysozyme and sodium carboxymethyl cellulose for 5-fluorouracil controlled release. Int. J. Pharm., 2013, 441(1-2), 721–727.

K. Yu,; X. Y. Yang,; L. H. He,; R. Zheng,; J. Min,; H. Y. Su,; S. Y. Shan,; Q. M Jia,. Facile preparation of pH/reduction dual-stimuli responsive dextran nanogel as environment-sensitive carrier of doxorubicin. Polymer, 2020, 200, 122585.

K. Raemdonck,; T. G. Van Thienen,; R. E. Vandenbroucke,; N. N. Sanders,; J. Demeester,; S. C De Smedt,. Dextran microgels for time-controlled delivery of siRNA. Adv. Funct. Mater., 2008, 18(7), 993–1001.

M. J. Javid-Naderi,; A. Mahmoudi,; P. Kesharwani,; T. Jamialahmadi,; A Sahebkar,. Recent advances of nanotechnology in the treatment and diagnosis of polycystic ovary syndrome. J. Drug Deliv. Sci. Technol., 2023, 79, 104014.

林勰鹏. 基于多糖衍生物的微纳米药物载体的研究. 温州: 温州大学, 2011.

S. Y. Huang,; G. L Huang,. Preparation and drug delivery of dextran-drug complex. Drug Deliv., 2019, 26(1), 252–261.

T. G. Barclay,; C. M. Day,; N. Petrovsky,; S Garg,. Review of polysaccharide particle-based functional drug delivery. Carbohydr. Polym., 2019, 221, 94–112.

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

天然多糖类纳米凝胶药物载体的研究进展

基于ATRP法研制多糖基因载体

O-羧甲基壳聚糖的制备及应用研究进展

同载基因和药物的超微载体粒子的制备及体外评价