Full Text:   <1295>

Summary:  <1221>

Suppl. Mater.: 

CLC number: R94; TB383

On-line Access: 2020-07-07

Received: 2019-12-08

Revision Accepted: 2020-03-20

Crosschecked: 2020-06-05

Cited: 0

Clicked: 2361

Citations:  Bibtex RefMan EndNote GB/T7714


Xiao Liu


-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2020 Vol.21 No.7 P.571-580


Hyaluronic acid derivative-modified nano-structured lipid carrier for cancer targeting and therapy

Author(s):  Xiao Liu, Hai Liu, Su-lan Wang, Jing-wen Liu

Affiliation(s):  Department of Pharmacy, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; more

Corresponding email(s):   3415120@zju.edu.cn

Key Words:  Paclitaxel (PTX), Hyaluronic acid-octadecylamine (HA-ODA), Nano-structured lipid carrier (NLC), Tumor targeting, In vivo distribution

Xiao Liu, Hai Liu, Su-lan Wang, Jing-wen Liu. Hyaluronic acid derivative-modified nano-structured lipid carrier for cancer targeting and therapy[J]. Journal of Zhejiang University Science B, 2020, 21(7): 571-580.

@article{title="Hyaluronic acid derivative-modified nano-structured lipid carrier for cancer targeting and therapy",
author="Xiao Liu, Hai Liu, Su-lan Wang, Jing-wen Liu",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Hyaluronic acid derivative-modified nano-structured lipid carrier for cancer targeting and therapy
%A Xiao Liu
%A Hai Liu
%A Su-lan Wang
%A Jing-wen Liu
%J Journal of Zhejiang University SCIENCE B
%V 21
%N 7
%P 571-580
%@ 1673-1581
%D 2020
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900624

T1 - Hyaluronic acid derivative-modified nano-structured lipid carrier for cancer targeting and therapy
A1 - Xiao Liu
A1 - Hai Liu
A1 - Su-lan Wang
A1 - Jing-wen Liu
J0 - Journal of Zhejiang University Science B
VL - 21
IS - 7
SP - 571
EP - 580
%@ 1673-1581
Y1 - 2020
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900624

To reduce the problems of poor solubility, high in vivo dosage requirement, and weak targeting ability of paclitaxel (PTX), a hyaluronic acid-octadecylamine (HA-ODA)-modified nano-structured lipid carrier (HA-NLC) was constructed. HA-ODA conjugates were synthesized by an amide reaction between HA and ODA. The hydrophobic chain of HA-ODA can be embedded in the lipid core of the NLC to obtain HA-NLC. The HA-NLC displayed strong internalization in cluster determinant 44 (CD44) highly expressed MCF-7 cells, and endocytosis mediated by the CD44 receptor was involved. The HA-NLC had an encapsulation efficiency of PTX of 72.0%. The cytotoxicity of the PTX-loaded nanoparticle HA-NLC/PTX in MCF-7 cells was much stronger than that of the commercial preparation Taxol®. In vivo, the HA-NLC exhibited strong tumor targeting ability. The distribution of the NLCs to the liver and spleen was reduced after HA modification, while more nanoparticles were aggregated to the tumor site. Our results suggest that HA-NLC has excellent properties as a nano drug carrier and potential for in vivo targeting.




Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1]Agrawal M, Ajazuddin, Tripathi DK, et al., 2017. Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer’s disease. J Control Release, 260:61-77.

[2]Bourgeois-Daigneault MC, St-Germain LE, Roy DG, et al., 2016. Combination of paclitaxel and MG1 oncolytic virus as a successful strategy for breast cancer treatment. Breast Cancer Res, 18(1):83.

[3]Cai J, Fu JF, Li RR, et al., 2019. A potential carrier for anti- tumor targeted delivery-hyaluronic acid nanoparticles. Carbohydr Polym, 208:356-364.

[4]Chen HR, Huang XW, Wang ST, et al., 2015. Nab-paclitaxel (abraxane)-based chemotherapy to treat elderly patients with advanced non-small-cell lung cancer: a single center, randomized and open-label clinical trial. Chin J Cancer Res, 27(2):190-196.

[5]Chen J, Ouyang J, Chen QJ, et al., 2017. EGFR and CD44 dual-targeted multifunctional hyaluronic acid nanogels boost protein delivery to ovarian and breast cancers in vitro and in vivo. ACS Appl Mater Interfaces, 9(28):24140-24147.

[6]Chen Z, Deng S, Yuan D, et al., 2018. Novel nano-microspheres containing chitosan, hyaluronic acid, and chondroitin sulfate deliver growth and differentiation factor-5 plasmid for osteoarthritis gene therapy. J Zhejiang Univ-Sci B (Biomed & Biotechnol), 19(12):910-923.

[7]Eskandani M, Nazemiyeh H, 2014. Self-reporter shikonin-Act-loaded solid lipid nanoparticle: formulation, physicochemical characterization and geno/cytotoxicity evaluation. Eur J Pharm Sci, 59:49-57.

[8]Esposito E, Drechsler M, Mariani P, et al., 2017. Lipid nanoparticles for administration of poorly water soluble neuroactive drugs. Biomed Microdevices, 19(3):44.

[9]Giuffrida MC, Dosio F, Castelli F, et al., 2014. Lipophilic prodrug of paclitaxel: interaction with a dimyristoylphosphatidylcholine monolayer. Int J Pharm, 475(1-2):624-631.

[10]Hugo W, Zaretsky JM, Sun L, et al., 2016. Genomic and transcriptomic features of response to anti-PD-1 therapy in metastatic melanoma. Cell, 165(1):35-44.

[11]Jones SK, Sarkar A, Feldmann DP, et al., 2017. Revisiting the value of competition assays in folate receptor-mediated drug delivery. Biomaterials, 138:35-45.

[12]Kansu-Celik H, Gungor M, Ortac F, et al., 2017. Expression of CD44 variant 6 and its prognostic value in benign and malignant endometrial tissue. Arch Gynecol Obstet, 296(2):313-318.

[13]Knopf-Marques H, Pravda M, Wolfova L, et al., 2016. Hyaluronic acid and its derivatives in coating and delivery systems: applications in tissue engineering, regenerative medicine and immunomodulation. Adv Healthc Mater, 5(22):2841-2855.

[14]Liu JW, Meng TT, Yuan M, et al., 2016. MicroRNA-200c delivered by solid lipid nanoparticles enhances the effect of paclitaxel on breast cancer stem cell. Int J Nanomed, 11:6713-6725.

[15]Martens TF, Peynshaert K, Nascimento TL, et al., 2017. Effect of hyaluronic acid-binding to lipoplexes on intravitreal drug delivery for retinal gene therapy. Eur J Pharm Sci, 103:27-35.

[16]Noack A, Hause G, Mäder K, 2012. Physicochemical characterization of curcuminoid-loaded solid lipid nanoparticles. Int J Pharmaceut, 423(2):440-451.

[17]Qiu LP, Long MM, Chen DW, 2013. Hyaluronic acid-based carriers for tumor targeted delivery system. Acta Pharm Sin, 48(9):1376-1382 (in Chinese).


[19]Qiu LP, Zhu MQ, Huang Y, et al., 2016. Mechanisms of cellular uptake with hyaluronic acid-octadecylamine micelles as drug delivery nanocarriers. RSC Adv, 6(46):39896-39902.

[20]Qiu LP, Zhu MQ, Gong K, et al., 2017. pH-triggered degradable polymeric micelles for targeted anti-tumor drug delivery. Mater Sci Eng C, 78:912-922.

[21]Quader S, Liu X, Chen Y, et al., 2017. cRGD peptide-installed epirubicin-loaded polymeric micelles for effective targeted therapy against brain tumors. J Control Release, 258:56-66.

[22]Tran TH, Choi JY, Ramasamy T, et al., 2014. Hyaluronic acid-coated solid lipid nanoparticles for targeted delivery of vorinostat to CD44 overexpressing cancer cells. Carbohydr Polym, 114:407-415.

[23]Wickens JM, Alsaab HO, Kesharwani P, et al., 2017. Recent advances in hyaluronic acid-decorated nanocarriers for targeted cancer therapy. Drug Dis Today, 22(4):665-680.

[24]Wong KM, Horton KJ, Coveler AL, et al., 2017. Targeting the tumor stroma: the biology and clinical development of pegylated recombinant human hyaluronidase (PEGPH20). Curr Oncol Rep, 19(7):47.

[25]Yingchoncharoen P, Kalinowski DS, Richardson DR, 2016. Lipid-based drug delivery systems in cancer therapy: what is available and what is yet to come. Pharmacol Rev, 68(3):701-787.

[26]Yuan H, Chen J, Du YZ, et al., 2007. Studies on oral absorption of stearic acid SLN by a novel fluorometric method. Colloids Surf B Biointerfaces, 58(2):157-164.

[27]Zhang HB, Li W, Guo XM, et al., 2017. Specifically increased paclitaxel release in tumor and synergetic therapy by a hyaluronic acid-tocopherol nanomicelle. ACS Appl Mater Interfaces, 9(24):20385-20398.

[28]Zhong YN, Goltsche K, Cheng L, et al., 2016. Hyaluronic acid-shelled acid-activatable paclitaxel prodrug micelles effectively target and treat CD44-overexpressing human breast tumor xenografts in vivo. Biomaterials, 84:250-261.

[29]List of electronic supplementary materials

[30]Fig. S1 Zeta potential determination of the nanoparticles (NLC, NLC/PTX, HA-NLC, and HA-NLC/PTX)

[31]Fig. S2 Size distribution of the nanoparticles (NLC, NLC/PTX, HA-NLC, and HA-NLC/PTX) at the 10th day after they were prepared

Open peer comments: Debate/Discuss/Question/Opinion


Please provide your name, email address and a comment

Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2022 Journal of Zhejiang University-SCIENCE