Hyaluronic acid (HA), as a critical ingredient of extracellular matrix (ECM) and synovial fluid, has attracted extensive attention in targeted tumor thearpy. The superiority of HA is reflected as its great biocompatibility, biodegradability and special binding ability to CD44 receptor. Moreover, CD44 receptor proteins are overexpressed in many kinds of tumor cells and cancer stem cells (CSCs). Therefore, HA is commonly used as ligands for the surface modification of versatile nanocarriers applied in various tumor therapy approaches.
Methods:
We reviewed the literature and summarized the unique properties of HA, the rationale for the use of HA as tumor-specific carrier for drug delivery, catabolism of HA coated nanocarriers, and research achievements of frequently-used HA-modified organic and inorganic nanocarries.
Results:
We concluded the significant applications of HA coated nanocarriers in tumor chemotherapy and chemoresistance, combination therapy and cancer theranostics.
Conclusion:
The application prospect of HA-coated nanocarriers will be more extensive for various targeting combination therapy and theranostics.
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References
1.
KnudsonW, LoeserRF. CD44 and integrin matrix receptors participate in cartilage homeostasis. Cell Mol Life Sci, 2002; 59(1):36–44.
2.
IwasakiN, KasaharaY, YamaneS, et al.Chitosan-based hyaluronic acid hybrid polymer fibers as a scaffold biomaterial for cartilage tissue engineering. Polymers, 2010; 3(1):100–113.
3.
KimSE, LeeJY, ShimKS, et al.Attenuation of inflammation and cartilage degradation by sulfasalazine-containing hyaluronic acid on osteoarthritis rat model. Int J Biol Macromol, 2018; 114:341–348.
4.
SongY, CaiH, YinTJ, et al.Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin E succinate conjugates for improved lung cancer treatment. Int J Nanomedicine, 2018; 13:1585–1600.
5.
ParkJ, KuM, KimE, et al.CD44-specific supramolecular hydrogels for fluorescence molecular imaging of stem-like gastric cancer cells. Integr Biol (Camb), 2013; 5(4):669–672.
6.
ZhangLW, GaoS, ZhangF, et al.Activatable hyaluronic acid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy. ACS Nano, 2014; 8(12):12250–12258.
7.
CohenK, EmmanuelR, Kisin-FinferE, et al.Modulation of drug resistance in ovarian adenocarcinoma using chemotherapy entrapped in hyaluronan-grafted nanoparticle clusters. ACS Nano, 2014; 8(3):2183–2195.
8.
BrodinNP, GuhaC, TomeWA. Photodynamic therapy and its role in combined modality anticancer treatment. Technol. Cancer Res Treat, 2015; 14(4):355–368.
9.
FangZZ, LiXY, XuZY, et al.Hyaluronic acid-modifified mesoporous silica-coated superparamagnetic Fe3O4 nanoparticles for targeted drug delivery. Int J Nanomedicine, 2019; 14:5785–5797.
10.
YadavAK, AgarwalA, RaiG, et al.Development and characterization of hyaluronic acid decorated PLGA nanoparticles for delivery of 5-fluorouracil. Drug Deliv, 2010; 17(8):561–572.
11.
SalwowskaNM, BebenekKA, ŻądłoDA, et al.Physiochemical properties and application of hyaluronic acid: A systematic review. J Cosmet Dermatol, 2016; 15(4):520–526.
12.
YunYH, GoetzDJ, YellenP, et al.Hyaluronan microspheres for sustained gene delivery and site-specific targeting. Biomaterials, 2004; 25(1):147–157.
13.
RostamiS, ParsianH. Hyaluronic Acid: From biochemical characteristics to its clinical translation in assessment of liver fibrosis. Hepat Mon, 2013; 13(12):e13787; doi: 10.5812/hepatmon.13787
14.
HuY, ChenX, XuYY, et al.Hierarchical assembly of hyaluronan coated albumin nanoparticles for pancreatic cancer chemoimmunotherapy. Nanoscale, 2019; 11(35):16476–16487.
15.
LouderboughJM, SchroederJA. Understanding the dual nature of CD44 in breast cancer progression. Mol Cancer Res, 2011; 9(12):1573–1586.
16.
MisraS, HeldinP, HascallVC, et al.Hyaluronan-CD44 interactions as potential targets for cancertherapy. Febs J, 2011; 278(9):1429–1443.
17.
MarhabaR, ZollerM. CD44 in cancer progression: Adhesion, migration and growth regulation. J Mol Histol, 2004; 35(3):211–231.
18.
LeiC, LiuXR, ChenQB, et al.Hyaluronic acid and albumin based nanoparticles for drug delivery. J Control Release, 2021; 331:416–433.
19.
ZollerM. CD44: Can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer, 2011; 11(4):254–267.
20.
LoboNA, ShimonoY, QianD, et al.The biology of cancer stem cells. Annu Rev Cell Dev Biol, 2007; 23:675–699.
21.
HurtEM, KawasakiBT, KlarmannGJ, et al.CD44 + CD24(-)prostate cells are early cancer progenitor/stem cells that provide a model for patients with poor prognosis. Br J Cancer, 2008; 98(4):756–765.
22.
IdowuMO, KmieciakM, DumurC, et al.CD44(+)/CD24(-/low) cancer stem/progenitor cells are more abundant in triple-negative invasive breast carcinoma phenotype and are associated with poor outcome. Hum Pathol, 2012; 43(3):364–373.
23.
LiY, ShiSJ, MingY, et al.Specific cancer stem cell-therapy by albumin nanoparticles functionalized with CD44-mediated targeting. J Nanobiotechnol, 2018; 16(1):99.
24.
HiscoxS, BaruhaB, SmithC, et al.Overexpression of CD44 accompanies acquired tamoxifen resistance in MCF7 cells and augments their sensitivity to the stromal factors, heregulin and hyaluronan. BMC Cancer, 2012; 12:458.
25.
ResnickNM, ClarkeMR, SiegfriedJM, et al.Expression of the cell adhesion molecule CD44 in human lung tumors and cell lines. Mol Diagn, 1998; 3(2):93–103.
26.
PennoMB, AugustJT, BaylinSB, et al.Expression of CD44 in human lung tumors. Cancer Res, 1994; 54(5):1381–1387.
27.
WeiHJ, YinT, ZhuZ, et al.Expression of CD44, CD24 and ESA in pancreatic adenocarcinoma cell lines varies with local microenvironment. Hepatobiliary Pancreat Dis Int, 2011; 10(4):428–434.
28.
WhatcottCJ, HanH, PosnerRG, et al.Targeting the tumor microenvironment in cancer: Why hyaluronidase deserves a second look. Cancer Discov, 2011; 1(4):291–296.
29.
HerreraLC, ShastriVP. Silencing of GFP expression in human mesenchymal stem cells using quaternary polyplexes of siRNA-PEI with glycosaminoglycans and albumin. Acta Biomater, 2019; 99:397–411.
30.
MattheolabakisG, MilaneL, SinghA, et al.Hyaluronic acid targeting of CD44 for cancer therapy: From receptor biology to nanomedicine. J Drug Target, 2015; 23(7–8):605–618.
31.
CsokaAB, FrostGI, SternR. The six hyaluronidase-like genes in the human and mouse genomes. Matrix Biol, 2001; 20(8):499–508.
32.
CultyM, NguyenHA, UnderhillCB. The hyaluronan receptor (CD44) participates in the uptake and degradation of hyaluronan. J Cell Biol, 1992; 116(4):1055–1062.
33.
HuaQ, KnudsonCB, KnudsonW. Internalization of hyaluronan by chondrocytes occurs via receptor-mediated endocytosis. J Cell Sci, 1993; 106 (Pt 1):365–375.
34.
KratzF, ElsadekB. Clinical impact of serum proteins on drug delivery. J Control Release, 2012; 161(2):429–445.
35.
KoopaeiMN, DinarvandR, AminiM, et al.Docetaxel immunonanocarriers as targeted delivery systems for HER2-positive tumor cells: Preparation, characterization, and cytotoxicity studies. Int J Nanomedicine, 2011; 6:1903e12–1901912; doi: 10.2147/IJN.S23211
36.
GuoS, LinCM, XuZ, et al.Co-delivery of cisplatin and rapamycin for enhanced anticancer therapy through synergistic effects and microenvironment modulation. ACS Nano., 2014; 8(5):4996–5009.
37.
Brannon-PeppasL, BlanchetteJO. Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev, 2004; 56(11):1649–1659.
38.
WangH, ZhengL, PengC, et al.Folic acid-modifified dendrimer entrapped gold nanoparticles as nanoprobes for targeted CT imaging of human lung adencarcinoma. Biomaterials, 2013; 34(2):470–480.
39.
QiX, FanY, HeH, et al.Hyaluronic acid-grafted polyamidoamine dendrimers enable long circulation and active tumor targeting simultaneously. Carbohydr Polym, 2015; 126:231–239.
40.
LiYY, ShiSJ, MingY, et al.Specifc cancer stem cell-therapy by albumin nanoparticles functionalized with CD44-mediated targeting. J Nanobiotechnol, 2018; 16(99):1–15.
41.
SkandalisSS, KaralisTT, ChatzopoulosA, et al.Hyaluronan-CD44 axis orchestrates cancer stem cell functions. Cell Signal, 2019; 63:109377.
42.
NicholsonAG, TsaoMS, BeasleyMB, et al.The 2021 WHO classification of lung tumors: Impact of advances since 2015. J Thoracic Oncol, 2022; 17(3):362–387.
43.
ChenX, WangM, HuY, et al.Low-dose paclitaxel via hyaluronan-functionalized bovine serum albumin nanoparticulate assembly for metastatic melanoma treatment. J Mater Chem B, 2020; 8(10):2139–2147.
44.
LangerK, BalthasarS, VogelV, et al.Optimization of the preparation process for human serum albumin (HSA) nanoparticles. Int J Pharm, 2003; 257(1–2):169–180.
45.
ShenYZ, LiWT. HA/HSA co-modified erlotinib–albumin nanoparticles for lung cancer treatment. Drug Des Devel Ther, 2018; 12:2285–2292.
46.
ByeonY, LeeJW, ChoiWS, et al.CD44-targeted PLGA nanoparticles incorporating paclitaxel and FAK siRNA overcome chemoresistance in epithelial ovarian cancer. Cancer Res, 2018; 78(21):6247–6256.
47.
ShiSJ, ZhouM, LiX, et al.Synergistic active targeting of dually integrin αvβ3/CD44- targeted nanoparticles to B16F10 tumors located at different sites of mouse bodies. J Control Release, 2016; 235:1–13.
48.
SongSS, ChenF, QiH, et al.Multifunctional tumor-targeting nanocarriers based on hyaluronic acid-mediated and pH-sensitive properties for efficient delivery of docetaxel. Pharm Res, 2014; 31(4):1032–1045.
49.
XuQB, ZhanGT, ZhangZL, et al.Manganese porphyrin-based metal-organic framework for synergistic sonodynamic therapy and ferroptosis in hypoxic tumors. Theranostics, 2021; 11(4):1937–1952.
50.
LiuJ, MukherjeeS, WangF, et al.Homochiral metal-organic frameworks for enantioseparation. Chem Soc Rev, 2021; 50(9):5706–5745.
51.
LinW, HuQ, JiangK, et al.A porphyrin-based metal–organic framework as a pH-responsive drug carrier. J Solid State Chem, 2016; 237:307–312.
52.
WangT, HuJ, LuoH, et al.Photosensitizer and autophagy promoter coloaded ROS-Responsive Dendrimer-Assembled carrier for synergistic enhancement of tumor growth suppression. Small, 2018; 14(38):e1802337; doi: 10.1002/smll.201802337
53.
WeinbergF, RamnathN, NagrathD. Reactive oxygen species in the tumor microenvironment: An overview. Cancers (Basel), 2019; 11(8):1191.
54.
SadeghiF, KardarGA, BolouriMR, et al.Overexpression of bHLH domain of HIF-1 failed to inhibit the HIF-1 transcriptional activity in hypoxia. Biol Res, 2020; 53(1):25.
55.
ZhangY, LiaoY, TangQ, et al.Biomimetic Nanoemulsion for synergistic photodynamic- immunotherapy against hypoxic breast tumor. Angew Chem Int Ed Engl, 2021; 60(19):10647–10653.
56.
YangZB, LuoY, YuH, et al.Reshaping the tumor immune microenvironment based on a light-activated nanoplatform for efffcient cancer therapy. Adv Mater, 2022; 34(11):e2108908.
57.
FanGL, DengFA, ZhouX, et al.Plasma membrane targeted photodynamic O2 economizer for hypoxic tumor therapy. Biomaterials, 2021; 273:120854.
58.
WangH, ChaoY, LiuJ, et al.Photosensitizercrosslinked in-situ polymerization on catalase for tumor hypoxia modulation & enhanced photodynamic therapy. Biomaterials, 2018; 181:310–317.
59.
LiY, SunP, ZhaoL, et al.Ferric ion driven assembly of catalase-like supramolecular photosensitizing Nanozymes for combating hypoxic tumors. Angew Chem Int Ed Engl, 2020; 59(51):23228–23238.
60.
CuiY, ChenX, ChengY, et al.CuWO4 Nanodots for NIR-induced photodynamic and Chemodynamic synergistic therapy. ACS Appl Mater Interfaces, 2021; 13(19):22150–22158.
61.
DengLD, FengZJ, DengHZ, et al.Rational design of nanoparticles to overcome poor tumor penetration and hypoxia-induced chemotherapy resistance: Combination of optimizing size and self-inducing high level of reactive oxygen species. ACS Appl Mater Interfaces, 2019; 11(35):31743–31754.
62.
HuJ, WuWR, QinYF, et al.Fabrication of Glyco-metal-organic frameworks for targeted interventional photodynamic/chemotherapy for hepatocellular carcinoma through percutaneous Transperitoneal puncture. Adv Funct Mater, 2020; 30:1910084.
63.
ZhangXD, ChenXK, GuoYX, et al.Dual gate-controlled therapeutics for overcoming bacterium-induced drug resistance and potentiating Cancer immunotherapy. Angew Chem Int Ed Engl, 2021; 60(25):14013–14021.
64.
BaiY, WangRQ, WangXN, et al.Hyaluronic acid coated nano-particles for H2O2-elevation augmented photo-/chemodynamic therapy. Int J Biol Macromol, 2023; 245:125523.
65.
LiRX, HeYW, ZhangSY, et al.Cell membrane-based nanoparticles: A new biomimetic platform for tumor diagnosis and treatment. Acta Pharm Sin B, 2018; 8(1):14–22.
66.
HanY, GaoC, WangH, et al.Macrophage membrane-coated nanocarriers co-modified by RVG29 and TPP improve brain neuronal mitochondria-targeting and therapeutic efficacy in Alzheimer’s disease mice. Bioact. Mater, 2020; 6(2):529–542.
67.
PengJR, YangQ, LiWT, et al.Erythrocyte-membrane-coated prussian blue/Manganese dioxide nanoparticles as H2O2 Responsive oxygen generator to enhance cancer chemotherapy/photothermal therapy. ACS Appl Mater Interfaces, 2017; 9(51):44410–44422.
68.
ShiJ, KundratL, PisheshaN, et al.Engineered red blood cells as carriers for systemic delivery of a wide array of functional probes. Proc Natl Acad Sci U S A, 2014; 111(28):10131–10136.
69.
BarhaghtalabRH, AiyelabeganHT, MalekiH, et al.Recent advances with erythrocytes as therapeutics carriers. Int J Pharmaceutics, 2024; doi: 10.1016/j.ijpharm.2024.124658
70.
PriceLSL, SternST, DealAM, et al.A reanalysis of nanoparticle tumor delivery usingclassical pharmacokinetic metrics. Sci Adv, 2020; 6(29):eaay9249; doi: 10.1126/sciadv.aay9249
71.
ZhangYT, XiaQ, WuT, et al.A novel multi-functionalized multicellular nanodelivery system for non-small cell lung cancer photochemotherapy. J Nanobiotechnology, 2021; 19(1):245.
72.
ZhangJ, SunYJ, TianBC, et al.Multifunctional mesoporous silica nanoparticles modified with Tumor-shedable hyaluronic acid as carriers for Doxorubicin. Colloids Surf B Biointerfaces, 2016; 144:293–302.
73.
ZhouYM, ChangC, LiuZH, et al.Hyaluronic acid-functionalized hollow mesoporous silica nanoparticles as pH-Sensitive nanocarriers for cancer chemophotodynamic therapy. Langmuir, 2021; 37(8):2619–2628.
74.
FuGL, LiuW, FengSS, et al.Prussian blue nanoparticles operate as a new generation of photothermal ablation agents for cancer therapy. Chem Commun (Camb), 2012; 48(94):11567–11569.
75.
ChengL, GongH, ZhuWW, et al.PEGylated Prussian blue nanocubes as a theranostic agent for simultaneous cancer imaging and photothermal therapy. Biomaterials, 2014; 35(37):9844–9852.
76.
JingLJ, ShaoSM, WangY, et al.Hyaluronic acid modified hollow prussian blue nanoparticles loading 10-hydroxycamptothecin for targeting thermochemotherapy of cancer. Theranostics, 2016; 6(1):40–53.
77.
YangYB, JingLJ, LiXD, et al.Hyaluronic acid conjugated magnetic Prussian Blue@Quantum dot nanoparticles for cancer theranostics. Theranostics, 2017; 7(2):466–481.
78.
DavisME, ChenZ, ShinDM. Nanoparticle therapeutics: An emerging treatment modality for cancer. Nat Rev Drug Discov, 2008; 7(9):771–782.
79.
WiradharmaN, ZhangY, VenkataramanS, et al.Self-assembled polymer nanostructures for delivery of anticancer therapeutics. Nano Today, 2009; 4(4):302–317.
80.
KunjachanS, RychlikB, StormG, et al.Multidrug resistance: Physiological principles and nanomedical solutions. Adv Drug Deliv Rev, 2013; 65(13–14):1852–1865.
81.
MarkmanJL, RekechenetskiyA, HollerE, et al.Nanomedicine therapeutic approaches to overcome cancer drug resistance. Adv Drug Deliv Rev, 2013; 65(13–14):1866–1879.
82.
BaeYH, YinHQ. Stability issues of polymeric micelles. J Control Release, 2008; 131(1):2–4.
PetrosRA, DeSimoneJM. Strategies in the design of nanoparticles for therapeutic applications. Nat Rev Drug Discov, 2010; 9(8):615–627.
85.
DengC, JiangYJ, ChengR, et al.Biodegradable polymeric micelles for targeted and controlled anticancer drug delivery: Promises, progress and prospects. Nano Today, 2012; 7(5):467–480.
86.
MengFH, ChengR, DengC, et al.Intracellular drug release nanosystems. Mater Today, 2012; 15(10):436–442.
87.
LiY, GaoGH, LeeDS. Stimulus-sensitive polymeric nanoparticles and their applications as drug and gene carriers. Adv Healthc Mater, 2013; 2(3):388–417.
88.
ChengR, MengFH, DengC, et al.Dual and multi-stimuli responsive polymeric nanoparticles for programmed site-specific drug delivery. Biomaterials, 2013; 34(14):3647–3657.
89.
WuYQ, LiJW, LiuL, et al.Hyaluronic acid nanoparticles for targeted oral delivery of doxorubicin: Lymphatic transport and CD44 engagement. Int J Biol Macromol, 2024; 273(Pt 2):133063.
90.
NowakAK, RobinsonBWS, LakeRA. Synergy between chemotherapy and immunotherapy in the treatment of established murine solid tumors. Cancer Res, 2003; 63(15):4490–4496.
91.
LiXD, LiangXL, MaF, et al.Chitosan stabilized Prussian blue nanoparticles for photothermally enhanced gene delivery. Colloids Surf B Biointerfaces, 2014; 123:629–638.
92.
ZhuWW, LiuK, SunXQ, et al.Mn2+-Doped Prussian Blue Nanocubes for Bimodal Imaging and Photothermal Therapy with Enhanced Performance. ACS Appl Mater Interfaces, 2015; 7(21):11575–11582.
93.
ZhangG, LuR, WuM, et al.Colorectal cancer-associated∼6kDa hyluronan serves as a novel biomarker for cancer progression and metastasis. FEBS J, 2019; 286(16):3148–3163.
94.
DonelanW, Dominguez-GutierrezPR, KusmartsevS. Deregulated hyaluronan metabolism in the tumor microenvironment drives cancer inflammation and tumor-associated immune suppresion. Front Immunol, 2022; 13:971278.
95.
VasvaniS, KulkarniP, RawtaniD. Hyaluronic acid: A review on its biology, aspects of drug delivery, route of administrations and a special emphasis on its approved marketed products and recent clinical studies. Int J Biol Macromol, 2020; 151:1012–1029.
