Dataset Information

Hyaluronic Acid-Decorated Laponite^® Nanocomposites for Targeted Anticancer Drug Delivery.

ABSTRACT: In this study, hyaluronic acid (HA), a natural polysaccharide that can specifically bind to CD44 receptors, was conjugated onto laponite^® (LAP) nanodisks for the encapsulation and specific delivery of the anti-cancer drug doxorubicin (DOX) to CD44-overexpressed cancer cells. The prepared LM-HA could encapsulate DOX efficiently and release drug in a continuous manner with pH-responsiveness. In vitro cell viability assay proved that LM-HA had good biocompatibility, and drug-loaded LM-HA/DOX exhibited targeted anti-tumor effects against HeLa cells with CD44 receptors overexpressed. In addition, the flow cytometric detection and confocal laser scanning microscope results confirmed that LM-HA/DOX could be specifically internalized by HeLa cells via CD44-mediated endocytosis. Therefore, the HA-modified LAP nanodisks with high drug loading efficiency, pH-sensitive drug release properties and CD44 targetability might be an efficient nanoplatform for cancer chemotherapy.

SUBMITTER: Jiang T

PROVIDER: S-EPMC6401931 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Hyaluronic Acid-Decorated Laponite<sup>®</sup> Nanocomposites for Targeted Anticancer Drug Delivery.

Jiang Tingting T Chen Guangxiang G Shi Xiangyang X Guo Rui R

Polymers 20190114 1

In this study, hyaluronic acid (HA), a natural polysaccharide that can specifically bind to CD44 receptors, was conjugated onto laponite<sup>®</sup> (LAP) nanodisks for the encapsulation and specific delivery of the anti-cancer drug doxorubicin (DOX) to CD44-overexpressed cancer cells. The prepared LM-HA could encapsulate DOX efficiently and release drug in a continuous manner with pH-responsiveness. In vitro cell viability assay proved that LM-HA had good biocompatibility, and drug-loaded LM-HA ...[more]

PMID: 30960121

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Project description:Doxorubicin (DOX) is one of the most commonly used antineoplastic agents, but its clinical application is oftentimes coupled with severe side effects. Selective delivery of DOX to tumors via nanosized drug carrier represents an attractive approach to this problem. Previously, we developed a dual functional nanomicellar carrier, PEG5K-embelin2 (PEG5K-EB2), which was able to deliver paclitaxel (PTX) selectively to tumors and to achieve an enhanced therapeutic effect. In the present study, we examined the utility of PEG5K-EB2 to deliver DOX to tumors. In addition, folic acid (FA) was coupled to the surface of the PEG5K-EB2 micelles (FA-PEG5K-EB2) to further improve the selective targetability of the system. DOX-loaded PEG5K-EB2 micelles were uniformly spherical particles with a diameter of approximately 20 nm. Incorporation of FA had minimal effect on the size of the particles. The DOX loading efficiency was as high as 91.7% and 93.5% for PEG5K-EB2 and FA-PEG5K-EB2, respectively. DOX formulated in PEG5K-EB2 micelles (with or without FA decoration) demonstrated sustained kinetics of DOX release compared to free DOX. FA-PEG5K-EB2 significantly facilitated the intracellular uptake of DOX over free DOX and PEGylated liposomal DOX (Doxil) in breast cancer cells, 4T1.2, and drug resistant cells, NCI/ADR-RES. P-gp ATPase assay showed that PEG5K-EB2 significantly inhibited the function of the P-gp efflux pump. The maximum tolerated dose of DOX-loaded PEG5K-EB2 micelles was 15 mg/kg in mice, which was 1.5-fold greater than that for free DOX. Pharmacokinetics (PK) and biodistribution studies showed that both types of DOX-loaded micelles, especially FA-PEG5K-EB2, were able to significantly prolong the blood circulation time of DOX and facilitate its preferential accumulation at the tumor tissue. Finally, DOX/PEG5K-EB2 mixed micelles demonstrated significantly enhanced tumor growth inhibitory effect with minimal toxicity in comparison to free DOX and Doxil and the antitumor activity was further enhanced after the decoration by folic acid. Our data suggest that FA-PEG5K-EB2 micelles represent a promising DOX delivery system that warrants more study in the future.

Dataset Information

Hyaluronic Acid-Decorated Laponite^® Nanocomposites for Targeted Anticancer Drug Delivery.

Publications

Hyaluronic Acid-Decorated Laponite<sup>®</sup> Nanocomposites for Targeted Anticancer Drug Delivery.

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Dataset Information

Hyaluronic Acid-Decorated Laponite® Nanocomposites for Targeted Anticancer Drug Delivery.

Publications

Hyaluronic Acid-Decorated Laponite<sup>®</sup> Nanocomposites for Targeted Anticancer Drug Delivery.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Hyaluronic Acid-Decorated Laponite^® Nanocomposites for Targeted Anticancer Drug Delivery.