Hyaluronan Endocytosis: Mechanisms of Uptake and Biological Functions

Racine, Ronny R.; Mummert, Mark E.

doi:10.5772/45976

Cited by 19 publications

(20 citation statements)

References 74 publications

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“…It is unknown why antibodyconjugated QDs were endocytosed, while organic molecule FITCconjugated antibodies remained on the plasma membrane. The size of the QD might be a determinant of endocytosis as it resembles the size of CD44 ligand hyaluronic acid [39], but further studies are needed to give a reasonable explanation.…”

Section: Discussionmentioning

confidence: 99%

“…To clarify whether anti-CD44-QDs engulfment was conditioned by receptor-mediated endocytosis [39], the analogous experiment was carried out in cells using anti-CD44 conjugated to FITC. As expected, the micrographs of MCF-7 cells showed a weak signal of anti-CD44-FITC ( Figure 5C) and a strong labeling of the membrane of MDA-MB-231 cells ( Figure 5D).…”

Section: Accumulation and Distribution Of Anti-cd44-qd Conjugatementioning

confidence: 99%

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Accumulation and Distribution of Non-targeted and Anti-CD44-conjugated Quantum Dots in Distinct Phenotypes of Breast Cancer

Steponkienė¹,

Dapkutė

Riekstiņa³

et al. 2015

J Nanomed Nanotechnol

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Background: It has been postulated that most if not all cancers are hierarchically organized and contain distinct phenotypes of cells. In breast tumors CD44 + /CD24 -/EpCAM + phenotype had been shown to possess the properties of cancer stem-like cells, while CD44low/ -/CD24 + /EpCAM + cells represent more differentiated tumor cells that are often classified as luminal subtype of cancer. Quantum dots had already been used for imaging in vitro and in vivo, however the information about accumulation and time-dependent distribution of antibody-conjugated quantum dots in different phenotypes of breast cancer is still missing. Results:The accumulation and distribution of QDs was compared between CD44low/ -/CD24 + /EpCAM + (MCF-7) and CD44 + /CD24 -/EpCam + (MDA-MB-231) cells. The accumulation of non-targeted QDs was twofold more efficient in CD44low/ -/CD24 + /EpCAM + cells than in CD44 + /CD24 -/EpCam + . Conjugation of anti-CD44 to QDs minimized uptake of QDs in CD44low/ -/CD24 + /EpCAM + cells thus showing the selectivity of this conjugate to CD44-positive cells. Most importantly, after 24 hours post labeling the membrane-bound anti-CD44-QDs was engulfed inside the cytoplasm of cells, while the conjugate of anti-CD44 and fluorescein isothiocyanate (FITC) remained on the cell membrane. Conclusion:The combination of QDs and antibodies gives a synergistic effect; antibody assures specific labeling of the desired cells while QDs initiate engulfment of the conjugate inside cells. Antibodies themselves are not capable of initiation of receptor-mediated endocytosis. Therefore these results are very important and might be used in the development of multifunctional agents for targeted labeling and delivery of bioactive compounds.

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Section: Discussionmentioning

confidence: 99%

Section: Accumulation and Distribution Of Anti-cd44-qd Conjugatementioning

confidence: 99%

Accumulation and Distribution of Non-targeted and Anti-CD44-conjugated Quantum Dots in Distinct Phenotypes of Breast Cancer

Steponkienė¹,

Dapkutė

Riekstiņa³

et al. 2015

J Nanomed Nanotechnol

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“…Such poor pharmacokinetics of free ZnPP was also confirmed in our previous studies [7,13]. Tumor tissue possesses the leaky vasculature and lack the functional lymph vessel, therefore long-circulating biocompatible polymer gradually accumulate in the tumor by enhanced permeability and retention (EPR) effect [18]. The hydrodynamic size of HA-ZnPP was large enough to evade the renal exclusion, and thus HA-ZnPP retained in the blood circulation much longer than that of free ZnPP (Figure 4).…”

Section: Body Distribution Of Ha-znpp In Tumor-bearing Micementioning

confidence: 51%

Hyaluronic Acid-zinc Protoporphyrin Conjugates for Photodynamic Antitumor Therapy

Eguchi¹,

Nakamura²,

Zhou³

et al. 2017

J Nanomed Nanotechnol

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“…Meanwhile, degradation of hyaluronic acid is controlled by multiple events. High molecular weight hyaluronic acid is degraded to smaller fragments by the extracellular hyaluronic acid-digesting enzyme, hyaluronidase 2 (Hyal 2) (Racine and Mummert, 2012). These fragments can be endocytosed by either receptor-mediated endocytosis (10 4 Da) or micropinocytosis (10 6 Da), depending on the molecular weight of the fragment.…”

Section: Receptor-mediated Endocytosismentioning

confidence: 99%

Targeted Drug Delivery via the Use of ECM-Mimetic Materials

Hwang

Sullivan

Kiick

2020

Front. Bioeng. Biotechnol.

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The use of drug delivery vehicles to improve the efficacy of drugs and to target their action at effective concentrations over desired periods of time has been an active topic of research and clinical investigation for decades. Both synthetic and natural drug delivery materials have facilitated locally controlled as well as targeted drug delivery. Extracellular matrix (ECM) molecules have generated widespread interest as drug delivery materials owing to the various biological functions of ECM. Hydrogels created using ECM molecules can provide not only biochemical and structural support to cells, but also spatial and temporal control over the release of therapeutic agents, including small molecules, biomacromolecules, and cells. In addition, the modification of drug delivery carriers with ECM fragments used as cell-binding ligands has facilitated celltargeted delivery and improved the therapeutic efficiency of drugs through interaction with highly expressed cellular receptors for ECM. The combination of ECM-derived hydrogels and ECM-derived ligand approaches shows synergistic effects, leading to a great promise for the delivery of intracellular drugs, which require specific endocytic pathways for maximal effectiveness. In this review, we provide an overview of cellular receptors that interact with ECM molecules and discuss examples of selected ECM components that have been applied for drug delivery in both local and systemic platforms. Finally, we highlight the potential impacts of utilizing the interaction between ECM components and cellular receptors for intracellular delivery, particularly in tissue regeneration applications.

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Hyaluronan Endocytosis: Mechanisms of Uptake and Biological Functions

Cited by 19 publications

References 74 publications

Accumulation and Distribution of Non-targeted and Anti-CD44-conjugated Quantum Dots in Distinct Phenotypes of Breast Cancer

Accumulation and Distribution of Non-targeted and Anti-CD44-conjugated Quantum Dots in Distinct Phenotypes of Breast Cancer

Hyaluronic Acid-zinc Protoporphyrin Conjugates for Photodynamic Antitumor Therapy

Targeted Drug Delivery via the Use of ECM-Mimetic Materials

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