scholarly journals Endosomal pH-Responsive Fe-Based Hyaluronate Nanoparticles for Doxorubicin Delivery

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3547
Author(s):  
Yangmun Bae ◽  
Yoonyoung Kim ◽  
Eun Seong Lee
Keyword(s):  
Hyaluronic Acid ◽  
Tumor Cells ◽  
Tumor Targeting ◽  
Drug Carriers ◽  
Acidic Environment ◽  
Ph Responsive ◽  
Ferrous Chloride ◽  
Endosomal Ph ◽  
Dimethylmaleic Anhydride ◽  
Positively Charged

In this study, we report pH-responsive metal-based biopolymer nanoparticles (NPs) for tumor-specific chemotherapy. Here, aminated hyaluronic acid (aHA) coupled with 2,3-dimethylmaleic anhydride (DMA, as a pH-responsive moiety) (aHA-DMA) was electrostatically complexed with ferrous chloride tetrahydrate (FeCl2/4H2O, as a chelating metal) and doxorubicin (DOX, as an antitumor drug model), producing DOX-loaded Fe-based hyaluronate nanoparticles (DOX@aHA-DMA/Fe NPs). Importantly, the DOX@aHA-DMA/Fe NPs improved tumor cellular uptake due to HA-mediated endocytosis for tumor cells overexpressing CD44 receptors. As a result, the average fluorescent DOX intensity observed in MDA-MB-231 cells (with CD44 receptors) was ~7.9 × 102 (DOX@HA/Fe NPs, without DMA), ~8.1 × 102 ([email protected]/Fe NPs), and ~9.3 × 102 ([email protected]/Fe NPs). Furthermore, the DOX@aHA-DMA/Fe NPs were destabilized due to ionic repulsion between Fe2+ and DMA-detached aHA (i.e., positively charged free aHA) in the acidic environment of tumor cells. This event accelerated the release of DOX from the destabilized NPs. Our results suggest that these NPs can be promising tumor-targeting drug carriers responding to acidic endosomal pH.

scholarly journals Transferrin-Conjugated pH-Responsive γ-Cyclodextrin Nanoparticles for Antitumoral Topotecan Delivery

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1109
Author(s):  
Seonyoung Yoon ◽  
Yoonyoung Kim ◽  
Yu Seok Youn ◽  
Kyung Taek Oh ◽  
Dongin Kim ◽  
...  
Keyword(s):  
Animal Studies ◽  
Endocytic Pathway ◽  
Drug Uptake ◽  
Ph Responsive ◽  
Mice Model ◽  
Tumor Cell Death ◽  
Endosomal Ph ◽  
Dimethylmaleic Anhydride ◽  
Poly Ethylene

In this study, we developed γ-cyclodextrin-based multifunctional nanoparticles (NPs) for tumor-targeted therapy. The NPs were self-assembled using a γ-cyclodextrin (γCD) coupled with phenylacetic acid (PA), 2,3-dimethylmaleic anhydride (DMA), poly(ethylene glycol) (PEG), and transferrin (Tf), termed γCDP-(DMA/PEG-Tf) NPs. These γCDP-(DMA/PEG-Tf) NPs are effective in entrapping topotecan (TPT, as a model antitumor drug) resulting from the ionic interaction between pH-responsive DMA and TPT or the host–guest interaction between γCDP and TPT. More importantly, the γCDP-(DMA/PEG-Tf) NPs can induce ionic repulsion at an endosomal pH (~6.0) resulting from the chemical detachment of DMA from γCDP, which is followed by extensive TPT release. We demonstrated that γCDP-(DMA/PEG-Tf) NPs led to a significant increase in cellular uptake and MDA-MB-231 tumor cell death. In vivo animal studies using an MDA-MB-231 tumor xenografted mice model supported the finding that γCDP-(DMA/PEG-Tf) NPs are effective carriers of TPT to Tf receptor-positive MDA-MB-231 tumor cells, promoting drug uptake into the tumors through the Tf ligand-mediated endocytic pathway and increasing their toxicity due to DMA-mediated cytosolic TPT delivery.

scholarly journals Schiff-Linked PEGylated Doxorubicin Prodrug Forming pH-Responsive Nanoparticles With High Drug Loading and Effective Anticancer Therapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Jian Song ◽  
Bingbing Xu ◽  
Hui Yao ◽  
Xiaofang Lu ◽  
Yang Tan ◽  
...  
Keyword(s):  
Drug Release ◽  
Tumor Cells ◽  
Drug Loading ◽  
Drug Carriers ◽  
Anticancer Therapy ◽  
Therapeutic Effects ◽  
Ph Responsive ◽  
High Drug ◽  
High Drug Loading ◽  
Mcf 7

Developing efficacious drug delivery systems for targeted cancer chemotherapy remains a major challenge. Here we demonstrated a kind of pH-responsive PEGylated doxorubicin (DOX) prodrug via the effective esterification and Schiff base reactions, which could self-assemble into the biodegradable micelles in aqueous solutions. Owing to low pH values inside the tumor cells, these PEG-Schiff-DOX nanoparticles exhibited high drug loading ability and pH-responsive drug release behavior within the tumor cells or tissues upon changes in physical and chemical environments, but they displayed good stability at physiological conditions for a long period. CCK-8 assay showed that these PEGylated DOX prodrugs had a similar cytotoxicity to the MCF-7 tumor cells as the free DOX drug. Moreover, this kind of nanoparticle could also encapsulate small DOX drugs with high drug loading, sufficient drug release and enhanced therapeutic effects toward MCF-7 cells, which will be benefited for developing more drug carriers with desirable functions for clinical anticancer therapy.

One-pot synthesis of acid-induced in situ aggregating theranostic gold nanoparticles with enhanced retention in tumor cells

2019 ◽  
Vol 7 (5) ◽  
pp. 2009-2022 ◽  
Author(s):  
Mingbo Cheng ◽  
Yahui Zhang ◽  
Xiaolei Zhang ◽  
Wei Wang ◽  
Zhi Yuan
Keyword(s):  
Gold Nanoparticles ◽  
Tumor Cells ◽  
Photothermal Therapy ◽  
Tumor Targeting ◽  
Acidic Environment ◽  
Dual Mode ◽  
One Pot ◽  
One Pot Synthesis

In this work, we took advantage of a one-pot reaction to prepare tumor-targeting nanoparticles (Au@T), which could respond to the intracellular acidic environment and form aggregates to enhance the retention effect of nanoparticles in tumor cells, for tumor dual-mode diagnose and photothermal therapy.

scholarly journals Tumor Microenvironment Responsive Pepper Mild Mottle Virus-Based Nanotubes for Targeted Delivery and Controlled Release of Paclitaxel

2021 ◽  
Vol 9 ◽  
Author(s):  
Jiejun Peng ◽  
Yueyan Yin ◽  
Hongze Liang ◽  
Yuwen Lu ◽  
Hongying Zheng ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Cells ◽  
Targeted Delivery ◽  
Plant Virus ◽  
Drug Carriers ◽  
Cell Uptake ◽  
Mottle Virus ◽  
Ph Responsive ◽  
Pepper Mild Mottle Virus ◽  
Strong Candidate

Plant virus nanoparticles (PVNPs) have been widely used for drug delivery, antibody development and medical imaging because of their good biodegradation and biocompatibility. Particles of pepper mild mottle virus (PMMoV) are elongated and may be useful as drug carriers because their shape favours long circulation, preferential distribution and increased cellular uptake. Moreover, its effective degradation in an acidic microenvironment enables a pH-responsive release of the encapsulated drug. In this study, genetic engineering techniques were used to form rod-shaped structures of nanoparticles (PMMoV) and folated-modified PMMoV nanotubes were prepared by polyethylene glycol (PEG) to provide targeted delivery of paclitaxel (PTX). FA@PMMoV@PTX nanotubes were designed to selectively target tumor cells and to release the encapsulated PTX in response to pH. Efficient cell uptake of FA@PMMoV@PTX nanotubes was observed when incubated with tumor cells, and FA@PMMoV@PTX nanotubes had superior cytotoxicity to free PTX, as reflected by cell survival and apoptosis. This system is a strong candidate for use in developing improved strategies for targeted treatment of tumors.

Tumor-targeting and pH-responsive nanoparticles from hyaluronic acid for the enhanced delivery of doxorubicin

2018 ◽  
Vol 113 ◽  
pp. 737-747 ◽  
Author(s):  
Jianhong Liao ◽  
Haoran Zheng ◽  
Zengming Fei ◽  
Bo Lu ◽  
Hua Zheng ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Tumor Targeting ◽  
Ph Responsive

Fabrication of Small Multifunctional CuS Nanoclusters for Fluorescence Imaging and Chemo-Photothermal Therapy of Cancer

NANO ◽  
2020 ◽  
Vol 15 (09) ◽  
pp. 2050123
Author(s):  
Yanqiu Zhao ◽  
Yang Zou ◽  
Xunxun Deng ◽  
Hanwen Wang ◽  
Shuo Wu
Keyword(s):  
Hyaluronic Acid ◽  
Real Time ◽  
Tumor Cells ◽  
Fluorescence Imaging ◽  
Photothermal Therapy ◽  
Colloid Stability ◽  
Ph Responsive ◽  
Ha Coating ◽  
Promising Application ◽  
Real Time Tracking

A multifunctional nanodrug, PAMAM@CuS-HA-RB/DOX, was prepared for the real time tracking and chemo-photothermal therapy of tumor cells. The CuS nanoclusters with diameter less than 10[Formula: see text]nm could be easily ingested by tumor cells and showed good colloid stability and high photothermal conversion efficiency. The hyaluronic acid (HA) coating and rhodamine B (RB) labeling endowed the nanocomposite with low cytotoxity and real time fluorescence imaging ability. In the acidic tumor microenvironment, the doxorubicin linked via the pH-responsive hydrazone bonds was released and worked synergistically with CuS to kill the tumor cells, which showed a high chemo-photothermal therapy capacity. All these properties indicated the PAMAM@CuS-HA-RB/DOX have promising application for the therapy of cancers and tracking of nanodrugs.

scholarly journals The cancer glycocalyx mediates intravascular adhesion and extravasation during metastatic dissemination

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Giovanni S. Offeddu ◽  
Cynthia Hajal ◽  
Colleen R. Foley ◽  
Zhengpeng Wan ◽  
Lina Ibrahim ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Vascular System ◽  
Migration And Invasion ◽  
Improve Patient Survival ◽  
Adhesive Interactions ◽  
Vitro Model ◽  
Metastatic Sites

AbstractThe glycocalyx on tumor cells has been recently identified as an important driver for cancer progression, possibly providing critical opportunities for treatment. Metastasis, in particular, is often the limiting step in the survival to cancer, yet our understanding of how tumor cells escape the vascular system to initiate metastatic sites remains limited. Using an in vitro model of the human microvasculature, we assess here the importance of the tumor and vascular glycocalyces during tumor cell extravasation. Through selective manipulation of individual components of the glycocalyx, we reveal a mechanism whereby tumor cells prepare an adhesive vascular niche by depositing components of the glycocalyx along the endothelium. Accumulated hyaluronic acid shed by tumor cells subsequently mediates adhesion to the endothelium via the glycoprotein CD44. Trans-endothelial migration and invasion into the stroma occurs through binding of the isoform CD44v to components of the sub-endothelial extra-cellular matrix. Targeting of the hyaluronic acid-CD44 glycocalyx complex results in significant reduction in the extravasation of tumor cells. These studies provide evidence of tumor cells repurposing the glycocalyx to promote adhesive interactions leading to cancer progression. Such glycocalyx-mediated mechanisms may be therapeutically targeted to hinder metastasis and improve patient survival.

scholarly journals Trospium Chloride Transport by Mouse Drug Carriers of the Slc22 and Slc47 Families

2020 ◽  
Vol 22 (1) ◽  
pp. 22
Author(s):  
Matthias Gorecki ◽  
Simon F. Müller ◽  
Regina Leidolf ◽  
Joachim Geyer
Keyword(s):  
Knockout Mouse ◽  
Organic Cation ◽  
Chloride Transport ◽  
Drug Carriers ◽  
Hek293 Cells ◽  
Low Permeability ◽  
Organic Cation Transporters ◽  
Trospium Chloride ◽  
Individual Role ◽  
Positively Charged

Background: The muscarinic receptor antagonist trospium chloride (TCl) is used for pharmacotherapy of the overactive bladder syndrome. TCl is a hydrophilic positively charged drug. Therefore, it has low permeability through biomembranes and requires drug transporters for distribution and excretion. In humans, the organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion MATE1 and MATE2-K carriers showed TCl transport. However, their individual role for distribution and excretion of TCl is unclear. Knockout mouse models lacking mOct1/mOct2 or mMate1 might help to clarify their role for the overall pharmacokinetics of TCl. Method: In preparation of such experiments, TCl transport was analyzed in HEK293 cells stably transfected with the mouse carriers mOct1, mOct2, mMate1, and mMate2, respectively. Results: Mouse mOct1, mOct2, and mMate1 showed significant TCl transport with Km values of 58.7, 78.5, and 29.3 µM, respectively. In contrast, mMate2 did not transport TCl but showed MPP+ transport with Km of 60.0 µM that was inhibited by the drugs topotecan, acyclovir, and levofloxacin. Conclusion: TCl transport behavior as well as expression pattern were quite similar for the mouse carriers mOct1, mOct2, and mMate1 compared to their human counterparts.

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