Hyaluronic Acid-Based Nanocarriers for Anticancer Drug Delivery

Overview

Journal Polymers (Basel)

Publisher MDPI

Date 2023 May 27

PMID 37242892

Authors

Chao-Ping Fu

Xing-Yu Cai

Si-Lin Chen

Hong-Wei Yu

Ying Fang

Xiao-Chen Feng

Li-Ming Zhang

Chang-Yong Li

Affiliations

Soon will be listed here.

Abstract

Hyaluronic acid (HA), a main component of the extracellular matrix, is widely utilized to deliver anticancer drugs due to its biocompatibility, biodegradability, non-toxicity, non-immunogenicity and numerous modification sites, such as carboxyl and hydroxyl groups. Moreover, HA serves as a natural ligand for tumor-targeted drug delivery systems, as it contains the endocytic HA receptor, CD44, which is overexpressed in many cancer cells. Therefore, HA-based nanocarriers have been developed to improve drug delivery efficiency and distinguish between healthy and cancerous tissues, resulting in reduced residual toxicity and off-target accumulation. This article comprehensively reviews the fabrication of anticancer drug nanocarriers based on HA in the context of prodrugs, organic carrier materials (micelles, liposomes, nanoparticles, microbubbles and hydrogels) and inorganic composite nanocarriers (gold nanoparticles, quantum dots, carbon nanotubes and silicon dioxide). Additionally, the progress achieved in the design and optimization of these nanocarriers and their effects on cancer therapy are discussed. Finally, the review provides a summary of the perspectives, the lessons learned so far and the outlook towards further developments in this field.

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References

Mansoori-Kermani A, Khalighi S, Akbarzadeh I, Niavol F, Motasadizadeh H, Mahdieh A . Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer. Mater Today Bio. 2022; 16:100349. PMC: 9304880. DOI: 10.1016/j.mtbio.2022.100349. View

Yao H, Sun L, Li J, Zhou X, Li R, Shao R . A Novel Therapeutic siRNA Nanoparticle Designed for Dual-Targeting CD44 and Gli1 of Gastric Cancer Stem Cells. Int J Nanomedicine. 2020; 15:7013-7034. PMC: 7522319. DOI: 10.2147/IJN.S260163. View

Cao A, Ma P, Yang T, Lan Y, Yu S, Liu L . Multifunctionalized Micelles Facilitate Intracellular Doxorubicin Delivery for Reversing Multidrug Resistance of Breast Cancer. Mol Pharm. 2019; 16(6):2502-2510. DOI: 10.1021/acs.molpharmaceut.9b00094. View

Qian Y, Liang X, Yang J, Zhao C, Nie W, Liu L . Hyaluronan Reduces Cationic Liposome-Induced Toxicity and Enhances the Antitumor Effect of Targeted Gene Delivery in Mice. ACS Appl Mater Interfaces. 2018; 10(38):32006-32016. DOI: 10.1021/acsami.8b12393. View

Zhang Y, Cui H, Zhang R, Zhang H, Huang W . Nanoparticulation of Prodrug into Medicines for Cancer Therapy. Adv Sci (Weinh). 2021; 8(18):e2101454. PMC: 8456229. DOI: 10.1002/advs.202101454. View

Datir S, Das M, Singh R, Jain S . Hyaluronate tethered, "smart" multiwalled carbon nanotubes for tumor-targeted delivery of doxorubicin. Bioconjug Chem. 2012; 23(11):2201-13. DOI: 10.1021/bc300248t. View

Lei C, Liu X, Chen Q, Li Y, Zhou J, Zhou L . Hyaluronic acid and albumin based nanoparticles for drug delivery. J Control Release. 2021; 331:416-433. DOI: 10.1016/j.jconrel.2021.01.033. View

Tavianatou A, Caon I, Franchi M, Piperigkou Z, Galesso D, Karamanos N . Hyaluronan: molecular size-dependent signaling and biological functions in inflammation and cancer. FEBS J. 2019; 286(15):2883-2908. DOI: 10.1111/febs.14777. View

Xu Z, Zheng W, Yin Z . Synthesis and optimization of a bifunctional hyaluronan-based camptothecin prodrug. Arch Pharm (Weinheim). 2014; 347(4):240-6. DOI: 10.1002/ardp.201300177. View

10.

Jeong G, Jeong Y, Nah J . Triggered doxorubicin release using redox-sensitive hyaluronic acid-g-stearic acid micelles for targeted cancer therapy. Carbohydr Polym. 2019; 209:161-171. DOI: 10.1016/j.carbpol.2019.01.018. View

11.

Quagliariello V, Gennari A, Jain S, Rosso F, Iaffaioli R, Barbarisi A . Double-responsive hyaluronic acid-based prodrugs for efficient tumour targeting. Mater Sci Eng C Mater Biol Appl. 2021; 131:112475. DOI: 10.1016/j.msec.2021.112475. View

12.

Cai S, Thati S, Bagby T, Diab H, Davies N, Cohen M . Localized doxorubicin chemotherapy with a biopolymeric nanocarrier improves survival and reduces toxicity in xenografts of human breast cancer. J Control Release. 2010; 146(2):212-8. PMC: 2918704. DOI: 10.1016/j.jconrel.2010.04.006. View

13.

Zhang W, Zhou Y, Yu N, Tang L, Zhu G, Shao Y . The Superior Anticancer Effect of Self-Assembled Paclitaxel Nanofibers is Mediated Through Co-Operation Between Enhanced Apoptosis and Autophagic Cell Death. J Biomed Nanotechnol. 2019; 14(2):379-388. DOI: 10.1166/jbn.2018.2480. View

14.

Zheng T, Xu N, Kan Q, Li H, Lu C, Zhang P . Wet-Spinning Assembly of Continuous, Highly Stable Hyaluronic/Multiwalled Carbon Nanotube Hybrid Microfibers. Polymers (Basel). 2019; 11(5). PMC: 6571791. DOI: 10.3390/polym11050867. View

15.

Hua S . Lipid-based nano-delivery systems for skin delivery of drugs and bioactives. Front Pharmacol. 2015; 6:219. PMC: 4588690. DOI: 10.3389/fphar.2015.00219. View

16.

Yin T, Wang Y, Chu X, Fu Y, Wang L, Zhou J . Free Adriamycin-Loaded pH/Reduction Dual-Responsive Hyaluronic Acid-Adriamycin Prodrug Micelles for Efficient Cancer Therapy. ACS Appl Mater Interfaces. 2018; 10(42):35693-35704. DOI: 10.1021/acsami.8b09342. View

17.

Ricci V, Zonari D, Cannito S, Marengo A, Scupoli M, Malatesta M . Hyaluronated mesoporous silica nanoparticles for active targeting: influence of conjugation method and hyaluronic acid molecular weight on the nanovector properties. J Colloid Interface Sci. 2018; 516:484-497. DOI: 10.1016/j.jcis.2018.01.072. View

18.

Luo Y, Prestwich G . Synthesis and selective cytotoxicity of a hyaluronic acid-antitumor bioconjugate. Bioconjug Chem. 1999; 10(5):755-63. DOI: 10.1021/bc9900338. View

19.

Jiang S, Li M, Hu Y, Zhang Z, Lv H . Multifunctional self-assembled micelles of galactosamine-hyaluronic acid-vitamin E succinate for targeting delivery of norcantharidin to hepatic carcinoma. Carbohydr Polym. 2018; 197:194-203. DOI: 10.1016/j.carbpol.2018.05.090. View

20.

Zhang C, Xu C, Gao X, Yao Q . Platinum-based drugs for cancer therapy and anti-tumor strategies. Theranostics. 2022; 12(5):2115-2132. PMC: 8899578. DOI: 10.7150/thno.69424. View