Exploring the relationship of hyaluronic acid molecular weight and active targeting efficiency for designing hyaluronic acid-modified nanoparticles

Liu, Zhong; Li, Yanying; Xu, Lu; Li, Qingsong; Zhao, Dongyang; Li, Zhenbao; Zhang, Huicong; Zhang, Haotian; Kan, Qiming; Sun, Jin; Zhang, He

doi:10.1016/j.ajps.2018.11.002

Cited by 41 publications

(35 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been found that the MW of HA regulates its diverse physio-pathological functions (Misra et al, 2015 ). A similar relationship has also been observed in nanostructures decorated with HA, where MW affected the targeting efficiency; the impact of HA MW on grafted liposomes have been reported by several authors (Arpicco et al, 2013 ; Mizrahy et al, 2014 ; Qhattal et al, 2014 ; Zhong et al, 2019 ) where the liposomal cellular uptake was improved with increasing of HA MW (5–8 <10–12 <175–350 kDa). Consequently, improved cytotoxic and in vivo activity against cancer models have been observed.…”

Section: Introductionsupporting

confidence: 76%

Effects of the Molecular Weight of Hyaluronic Acid in a Carbon Nanotube Drug Delivery Conjugate

et al. 2020

View full text Add to dashboard Cite

Hyaluronic acid (HA) is a ubiquitous biopolymer involved in many pathophysiological roles. One HA receptor, the cluster of differentiation CD44 protein, is often overexpressed in tumor cells. As such, HA has attracted considerable interest in the development of drug delivery formulations, given its intrinsic targetability toward CD44 overexpressing cells. The present study is focused on examining the correlation of HA molecular weight with its targetability properties. A library of conjugates obtained by linking the amino group of the phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) to the carboxylic residues of HA of different molecular weight (6.4, 17, 51, 200, and 1,500 kDa) were synthesized and fully characterized. The HA-DMPE conjugates were then used to non-covalently functionalize the highly hydrophobic single-walled carbon nanotubes (CNT), and further encapsulate the anticancer drug doxorubicin (DOX). Our results show that the complexes DOX/CNT/HA-DMPE maintain very good and stable dispersibility. Drug release studies indicated a pH-responsive release of the drug from the nanocarrier. Cell viability tests demonstrated that all HA modified CNTs have good biocompatibility, and specific targeting toward cells overexpressing the CD44 receptor. Among all the molecular weights tested, the 200 kDa HA showed the highest increase in cellular uptake and cytotoxic activity. All these promising attributes make CNT/HA200-DMPE a “smart” platform for tumor-targeted delivery of anticancer agents.

show abstract

Section: Introductionsupporting

confidence: 76%

Effects of the Molecular Weight of Hyaluronic Acid in a Carbon Nanotube Drug Delivery Conjugate

et al. 2020

View full text Add to dashboard Cite

show abstract

“…It is noted that these findings are consistent with those of previous reports on the use of HMWHA-IONPs as a MR contrast agent. 36 , 41 , 42 A quantitative analysis showed that the reduction in the image intensity for U87MG glioblastoma cells was higher than for NIH3T3 cells ( Figure 10B ). This result is to be expected since there are more CD44 receptors on the cellular membrane of cancer cells (glioblastoma) than on normal fibroblast cells, 8 , 26 , 27 and hence LMWHA-IONPs show a stronger targeting ability.…”

Section: Discussionmentioning

confidence: 99%

“… 28 A similar tendency is also observed when HA is used to modify nanoparticles. 36 Moreover, when using chemical methods to decompose HMWHA, it is difficult to precisely control the breakdown point on the long chain of HA molecules. 35 Thus, if the chemical reaction disturbs the structure related to the targeting site of CD44, for example, the biological effect of the treated HA molecules is significantly reduced.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of T2* Weighted MRI Imaging Sensitivity of U87MG Glioblastoma Cells Using γ-Ray Irradiated Low Molecular Weight Hyaluronic Acid-Conjugated Iron Nanoparticles

Huang¹,

Wu²,

Chou³

et al. 2021

IJN

View full text Add to dashboard Cite

Introduction It has been reported that low-molecular-weight hyaluronic acid (LMWHA) exhibits a potentially beneficial effect on cancer therapy through targeting of CD44 receptors on tumor cell surfaces. However, its applicability towards tumor detection is still unclear. In this regard, LMWHA-conjugated iron (Fe 3 O 4 ) nanoparticles (LMWHA-IONPs) were prepared in order to evaluate its application for enhancing the T2* weighted MRI imaging sensitivity for tumor detection. Methods LMWHA and Fe 3 O 4 NPs were produced using γ-ray irradiation and chemical co-precipitation methods, respectively. First, LMWHA-conjugated FITC was prepared to confirm the ability of LMWHA to target U87MG cells using fluorescence microscopy. The hydrodynamic size distribution and dispersion of the IONPs and prepared LMWHA-IONPs were analyzed using dynamic light scattering (DLS). In addition, cell viability assays were performed to examine the biocompatibility of LMWHA and LMWHA-IONPs toward U87MG human glioblastoma and NIH3T3 fibroblast cell lines. The ability of LMWHA-IONPs to target tumor cells was confirmed by detecting iron (Fe) ion content using the thiocyanate method. Finally, time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging and in vitro magnetic resonance imaging (MRI) were performed to confirm the contrast enhancement effect of LMWHA-IONPs. Results Florescence analysis results showed that LMWHA-FITC successfully targeted the surfaces of both tested cell types. The ability of LMWHA to target U87MG cells was higher than for NIH3T3 cells. Cell viability experiments showed that the fabricated LMWHA-IONPs possessed good biocompatibility for both cell lines. After co-culturing test cells with the LMWHA-IONPs, detected Fe ion content in the U87MG cells was much higher than that of the NIH3T3 cells in both thiocyanate assays and TOF-SIMs images. Finally, the addition of LMWHA-IONPs to the U87MG cells resulted in an obvious improvement in T2* weighted MR image contrast compared to control NIH3T3 cells. Discussion Overall, the present results suggest that LMWHA-IONPs fabricated in this study provide an effective MRI contrast agent for improving the diagnosis of early stage glioblastoma in MRI examinations.

show abstract

“…HA is an abundant GAG, deposited to most tissues’ ECM [ 160 ]. Its properties, biodegradation, biocompatibility, water-solubility, non-toxicity, and non-immunogenicity and its chemical characteristics, enabling modifications with functional groups, define HA as a suitable molecule carrier to deliver low molecular weight drugs [ 161 ]. Furthermore, its specific ligation with cell surface receptors such as CD44 and RHAMM [ 111 ] enables HA-based nanoparticles to target diseased cells that express these receptors.…”

Section: Types Of Nanoparticles and Materials Utilized For Targetementioning

confidence: 99%

Glycosaminoglycans: Carriers and Targets for Tailored Anti-Cancer Therapy

et al. 2021

View full text Add to dashboard Cite

The tumor microenvironment (TME) is composed of cancerous, non-cancerous, stromal, and immune cells that are surrounded by the components of the extracellular matrix (ECM). Glycosaminoglycans (GAGs), natural biomacromolecules, essential ECM, and cell membrane components are extensively altered in cancer tissues. During disease progression, the GAG fine structure changes in a manner associated with disease evolution. Thus, changes in the GAG sulfation pattern are immediately correlated to malignant transformation. Their molecular weight, distribution, composition, and fine modifications, including sulfation, exhibit distinct alterations during cancer development. GAGs and GAG-based molecules, due to their unique properties, are suggested as promising effectors for anticancer therapy. Considering their participation in tumorigenesis, their utilization in drug development has been the focus of both industry and academic research efforts. These efforts have been developing in two main directions; (i) utilizing GAGs as targets of therapeutic strategies and (ii) employing GAGs specificity and excellent physicochemical properties for targeted delivery of cancer therapeutics. This review will comprehensively discuss recent developments and the broad potential of GAG utilization for cancer therapy.

show abstract

Exploring the relationship of hyaluronic acid molecular weight and active targeting efficiency for designing hyaluronic acid-modified nanoparticles

Cited by 41 publications

References 56 publications

Effects of the Molecular Weight of Hyaluronic Acid in a Carbon Nanotube Drug Delivery Conjugate

Effects of the Molecular Weight of Hyaluronic Acid in a Carbon Nanotube Drug Delivery Conjugate

Enhancement of T2* Weighted MRI Imaging Sensitivity of U87MG Glioblastoma Cells Using γ-Ray Irradiated Low Molecular Weight Hyaluronic Acid-Conjugated Iron Nanoparticles

Glycosaminoglycans: Carriers and Targets for Tailored Anti-Cancer Therapy

Contact Info

Product

Resources

About