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The Clinical Potential of Targeted Nanomedicine: Delivering to Cancer Stem-like Cells

Cancer stem-like cells (CSCs) have been implicated in recurrence and treatment resistance in many human cancers. Thus, a CSC-targeted drug delivery strategy to eliminate CSCs is a desirable approach for developing a more effective anticancer therapy. We have developed a tumor-targeting nanodelivery... Full description

Journal Title: Molecular Therapy February 2014, Vol.22(2), pp.278-291
Main Author: Kim, Sang-Soo
Other Authors: Rait, Antonina , Rubab, Farwah , Rao, Abhi K , Kiritsy, Michael C , Pirollo, Kathleen F , Wang, Shangzi , Weiner, Louis M , Chang, Esther H
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 1525-0016 ; E-ISSN: 1525-0024 ; DOI: 10.1038/mt.2013.231
Link: https://www.sciencedirect.com/science/article/pii/S1525001616311492
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recordid: elsevier_sdoi_10_1038_mt_2013_231
title: The Clinical Potential of Targeted Nanomedicine: Delivering to Cancer Stem-like Cells
format: Article
creator:
  • Kim, Sang-Soo
  • Rait, Antonina
  • Rubab, Farwah
  • Rao, Abhi K
  • Kiritsy, Michael C
  • Pirollo, Kathleen F
  • Wang, Shangzi
  • Weiner, Louis M
  • Chang, Esther H
subjects:
  • Medicine
  • Biology
ispartof: Molecular Therapy, February 2014, Vol.22(2), pp.278-291
description: Cancer stem-like cells (CSCs) have been implicated in recurrence and treatment resistance in many human cancers. Thus, a CSC-targeted drug delivery strategy to eliminate CSCs is a desirable approach for developing a more effective anticancer therapy. We have developed a tumor-targeting nanodelivery platform (scL) for systemic administration of molecular medicines. Following treatment with the scL nanocomplex carrying various payloads, we have observed exquisite tumor-targeting specificity and significant antitumor response with long-term survival benefit in numerous animal models. We hypothesized that this observed efficacy might be attributed, at least in part, to elimination of CSCs. Here, we demonstrate the ability of scL to target both CSCs and differentiated nonstem cancer cells (non-CSCs) in various mouse models including subcutaneous and intracranial xenografts, syngeneic, and chemically induced tumors. We also show that systemic administration of scL carrying the wtp53 gene was able to induce tumor growth inhibition and the death of both CSCs and non-CSCs in subcutaneous colorectal cancer xenografts suggesting that this could be an effective method to reduce cancer recurrence and treatment resistance. This scL nanocomplex is being evaluated in a number of clinical trials where it has been shown to be well tolerated with indications of anticancer activity.
language: eng
source:
identifier: ISSN: 1525-0016 ; E-ISSN: 1525-0024 ; DOI: 10.1038/mt.2013.231
fulltext: fulltext
issn:
  • 1525-0016
  • 15250016
  • 1525-0024
  • 15250024
url: Link


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descriptionCancer stem-like cells (CSCs) have been implicated in recurrence and treatment resistance in many human cancers. Thus, a CSC-targeted drug delivery strategy to eliminate CSCs is a desirable approach for developing a more effective anticancer therapy. We have developed a tumor-targeting nanodelivery platform (scL) for systemic administration of molecular medicines. Following treatment with the scL nanocomplex carrying various payloads, we have observed exquisite tumor-targeting specificity and significant antitumor response with long-term survival benefit in numerous animal models. We hypothesized that this observed efficacy might be attributed, at least in part, to elimination of CSCs. Here, we demonstrate the ability of scL to target both CSCs and differentiated nonstem cancer cells (non-CSCs) in various mouse models including subcutaneous and intracranial xenografts, syngeneic, and chemically induced tumors. We also show that systemic administration of scL carrying the wtp53 gene was able to induce tumor growth inhibition and the death of both CSCs and non-CSCs in subcutaneous colorectal cancer xenografts suggesting that this could be an effective method to reduce cancer recurrence and treatment resistance. This scL nanocomplex is being evaluated in a number of clinical trials where it has been shown to be well tolerated with indications of anticancer activity.
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Cancer stem-like cells (CSCs) have been implicated in recurrence and treatment resistance in many human cancers. Thus, a CSC-targeted drug delivery strategy to eliminate CSCs is a desirable approach for developing a more effective anticancer therapy. We have developed a tumor-targeting nanodelivery platform (scL) for systemic administration of molecular medicines. Following treatment with the scL nanocomplex carrying various payloads, we have observed exquisite tumor-targeting specificity and significant antitumor response with long-term survival benefit in numerous animal models. We hypothesized that this observed efficacy might be attributed, at least in part, to elimination of CSCs. Here, we demonstrate the ability of scL to target both CSCs and differentiated nonstem cancer cells (non-CSCs) in various mouse models including subcutaneous and intracranial xenografts, syngeneic, and chemically induced tumors. We also show that systemic administration of scL carrying the wtp53 gene was able to induce tumor growth inhibition and the death of both CSCs and non-CSCs in subcutaneous colorectal cancer xenografts suggesting that this could be an effective method to reduce cancer recurrence and treatment resistance. This scL nanocomplex is being evaluated in a number of clinical trials where it has been shown to be well tolerated with indications of anticancer activity.

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