Multifunctional, CD44v6-Targeted ORMOSIL Nanoparticles Enhance Drugs Toxicity in Cancer Cells

Drug-loaded, PEGylated, organic-modified silica (ORMOSIL) nanoparticles prepared by microemulsion condensation of vinyltriethoxysilane (VTES) were investigated as potential nanovectors for cancer therapy. To target cancer stem cells, anti-CD44v6 antibody and hyaluronic acid (HA) were conjugated to amine-functionalized PEGylated ORMOSIL nanoparticles through thiol-maleimide and amide coupling chemistries, respectively. Specific binding and uptake of conjugated nanoparticles were studied on cells overexpressing the CD44v6 receptor. Cytotoxicity was subsequently evaluated in the same cells after the uptake of the nanoparticles. Internalization of nanocarriers loaded with the anticancer drug 3N-cyclopropylmethyl-7-phenyl-pyrrolo- quinolinone (MG2477) into cells resulted in a substantial increase of the cytotoxicity with respect to the free formulation. Targeting with anti-CD44v6 antibodies or HA yielded nanoparticles with similar effectiveness, in their optimized formulation.

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Hyaluronic acid-drug conjugate of docetaxel and metformin to target cancer cells and cancer stem cells: Synthesis and characterization

Journal of Controlled Release ◽

10.1016/j.jconrel.2013.08.122 ◽

2013 ◽

Vol 172 (1) ◽

pp. e59 ◽

Cited By ~ 2

Author(s):

Navid Goodarzi ◽

Mohsen Amini ◽

Mohammad Hossein Ghahremani ◽

Fatemeh Atyabi ◽

Seyed Nasser Ostad ◽

...

Keyword(s):

Stem Cells ◽

Hyaluronic Acid ◽

Cancer Stem Cells ◽

Cancer Cells ◽

Synthesis And Characterization ◽

Drug Conjugate ◽

Target Cancer

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PIK3C3 Inhibition Promotes Sensitivity to Colon Cancer Therapy by Inhibiting Cancer Stem Cells

Cancers ◽

10.3390/cancers13092168 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2168

Author(s):

Balawant Kumar ◽

Rizwan Ahmad ◽

Swagat Sharma ◽

Saiprasad Gowrikumar ◽

Mark Primeaux ◽

...

Keyword(s):

Stem Cells ◽

Colon Cancer ◽

Cancer Therapy ◽

Cancer Stem Cells ◽

Side Population ◽

Therapy Resistance ◽

Fluorescent Reporter ◽

Combination Treatments ◽

Gsk 3Β ◽

Resistance To Chemotherapy

Background: Despite recent advances in therapies, resistance to chemotherapy remains a critical problem in the clinical management of colorectal cancer (CRC). Cancer stem cells (CSCs) play a central role in therapy resistance. Thus, elimination of CSCs is crucial for effective CRC therapy; however, such strategies are limited. Autophagy promotes resistance to cancer therapy; however, whether autophagy protects CSCs to promote resistance to CRC-therapy is not well understood. Moreover, specific and potent autophagy inhibitors are warranted as clinical trials with hydroxychloroquine have not been successful. Methods: Colon cancer cells and tumoroids were used. Fluorescent reporter-based analysis of autophagy flux, spheroid and side population (SP) culture, and qPCR were done. We synthesized 36-077, a potent inhibitor of PIK3C3/VPS34 kinase, to inhibit autophagy. Combination treatments were done using 5-fluorouracil (5-FU) and 36-077. Results: The 5-FU treatment induced autophagy only in a subset of the treated colon cancer. These autophagy-enriched cells also showed increased expression of CSC markers. Co-treatment with 36-077 significantly improved efficacy of the 5-FU treatment. Mechanistic studies revealed that combination therapy inhibited GSK-3β/Wnt/β-catenin signaling to inhibit CSC population. Conclusion: Autophagy promotes resistance to CRC-therapy by specifically promoting GSK-3β/Wnt/β-catenin signaling to promote CSC survival, and 36-077, a PIK3C3/VPS34 inhibitor, helps promote efficacy of CRC therapy.

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Modeling the Treatment of Glioblastoma Multiforme and Cancer Stem Cells with Ordinary Differential Equations

Computational and Mathematical Methods in Medicine ◽

10.1155/2016/1239861 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Kristen Abernathy ◽

Jeremy Burke

Keyword(s):

Stem Cells ◽

Glioblastoma Multiforme ◽

Cancer Therapy ◽

Cancer Stem Cells ◽

Differential Equations ◽

Ordinary Differential Equations ◽

Cancer Patients ◽

Tumor Cells ◽

Tumor Recurrence ◽

Common Event

Despite improvements in cancer therapy and treatments, tumor recurrence is a common event in cancer patients. One explanation of recurrence is that cancer therapy focuses on treatment of tumor cells and does not eradicate cancer stem cells (CSCs). CSCs are postulated to behave similar to normal stem cells in that their role is to maintain homeostasis. That is, when the population of tumor cells is reduced or depleted by treatment, CSCs will repopulate the tumor, causing recurrence. In this paper, we study the application of the CSC Hypothesis to the treatment of glioblastoma multiforme by immunotherapy. We extend the work of Kogan et al. (2008) to incorporate the dynamics of CSCs, prove the existence of a recurrence state, and provide an analysis of possible cancerous states and their dependence on treatment levels.

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