Nanoparticle formulations of histone deacetylase inhibitors for effective chemoradiotherapy in solid tumors

Biomaterials
Edina C WangAndrew Z Wang

Abstract

Histone deacetylase inhibitors (HDACIs) represent a class of promising agents that can improve radiotherapy in cancer treatment. However, the full therapeutic potential of HDACIs as radiosensitizers has been restricted by limited efficacy in solid malignancies. In this study, we report the development of nanoparticle (NP) formulations of HDACIs that overcome these limitations, illustrating their utility to improve the therapeutic ratio of the clinically established first generation HDACI vorinostat and a novel second generation HDACI quisinostat. We demonstrate that NP HDACIs are potent radiosensitizers in vitro and are more effective as radiosensitizers than small molecule HDACIs in vivo using mouse xenograft models of colorectal and prostate carcinomas. We found that NP HDACIs enhance the response of tumor cells to radiation through the prolongation of γ-H2AX foci. Our work illustrates an effective method for improving cancer radiotherapy treatment.

References

Apr 16, 1998·The Journal of Biological Chemistry·E P RogakouW M Bonner
Mar 4, 2000·Journal of Controlled Release : Official Journal of the Controlled Release Society·H MaedaK Hori
Jul 18, 2002·Nature Reviews. Drug Discovery·Ricky W Johnstone
May 18, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·William Kevin KellyVictoria M Richon
Sep 11, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Kevin Camphausen, Philip J Tofilon
Nov 3, 2007·Nanomedicine·Eric M PridgenOmid C Farokhzad
Oct 15, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Andrew A Lane, Bruce A Chabner
Oct 15, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Richard L PiekarzSusan E Bates
Oct 29, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Janine ArtsPatrick Angibaud
Aug 4, 2010·Proceedings of the National Academy of Sciences of the United States of America·J-H LeePaul A Marks
May 12, 2012·Polymers·Hirenkumar K Makadia, Steven J Siegel
Jun 7, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Balaji VenugopalUdai Banerji

❮ Previous
Next ❯

Citations

Mar 12, 2016·Investigative and Clinical Urology·Vinoth-Kumar Lakshmanan
Sep 28, 2015·Journal of Nanobiotechnology·Tae Won KwakDae Hwan Kang
Sep 30, 2016·International Journal of Radiation Oncology, Biology, Physics·Xi TianAndrew Z Wang
Feb 10, 2017·Medicinal Research Reviews·Chiara ZagniAntonio Rescifina
Apr 8, 2017·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Yuying ZhaoXiqiang Liu
Aug 30, 2018·Advanced Materials·Jiani XieYuliang Zhao
Feb 15, 2019·Biomolecules·Philippe BertrandValérie Héroguez
May 18, 2019·Clinical Epigenetics·Annalisa RobertiAgustin F Fernandez
Feb 6, 2020·Cancers·Hélène LossonMarc Diederich
Jul 3, 2020·Chemical Communications : Chem Comm·Li WangAhu Yuan
Oct 28, 2017·Nature Reviews. Materials·Hongmin ChenXiaoyuan Chen
Jan 10, 2017·Cancer Nanotechnology·Yu MiAndrew Z Wang
Jun 26, 2020·Frontiers in Cell and Developmental Biology·Bin TuYongzhuo Huang
Jul 1, 2020·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·Moataz RedaWassana Yantasee
Sep 27, 2018·ACS Applied Materials & Interfaces·Wei JiangJun Wang
Dec 20, 2017·ACS Nano·Christopher M HartshornPiotr Grodzinski

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Cancer Epigenetics and Senescence (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may be involved in regulating senescence in cancer cells. This feed captures the latest research on cancer epigenetics and senescence.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Cancer Epigenetics & Metabolism (Keystone)

Epigenetic changes are present and dysregulated in many cancers, including DNA methylation, non-coding RNA segments and post-translational protein modifications. The epigenetic changes may or may not provide advantages for the cancer cells. This feed focuses on the relationship between cell metabolism, epigenetics and tumor differentiation.