Nanotechnologies for the treatment of colon cancer: From old drugs to new hope

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• 作者：Larissa Kotelevets^a ; ^b ; ^c ; ¹ ; Eric Chastre^b ; ^c ; ¹ ; Didier Desma&euml ; le^a ; Patrick Couvreur^a ; ^{patrick.couvreur@u-psud.fr" class="auth_mail" title="E-mail the corresponding author} ;
• 关键词：ABC transporter ; ATP-binding cassette transporter ; CAF ; cancer-associated fibroblasts ; CSCs ; cancer stem cells ; CTR1 ; Copper transporter 1 ; CIMP ; CpG island methylator phenotype ; CRC ; colorectal cancer ; DPD ; dihydropyrimidine dehydrogenase ; ECM ; extracellular matrix ; EMT ; epithelial-mesenchymal transition ; EPR ; enhanced permability and retension effect ; HGF ; hepatocyte growth factor ; HNPCC ; hereditary non polyposis colorectal cancer ; mCRC ; metastatic colorectal cancer ; MMPs ; matrix metalloprotei
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 November 2016
• 年：2016
• 卷：514
• 期：1
• 页码：24-40
• 全文大小：2816 K

文摘

Colorectal cancer is a wide-reaching health problem due to its incidence and to the high mortality rates. Adjuvant chemotherapies have considerably improved the prognosis and/or the overall survival of patients with locally advanced and metastatic cancers. Nevertheless, their efficiency remains limited due to intrinsic and emerging multidrug resistance (MDR) of cancer cells, and to major adverse effects and dose limiting toxicities. The present review discusses the knowledge of clinically relevant mechanisms of resistance to cytotoxic and targeted therapies for the treatment of colorectal cancer, and focuses on the benefit of nanomedicine approach to circumvent these processes. Nanomedicaments should allow extensive cancer cell drug loading independent on cell surface transporters, −thus overwhelming drug metabolism and efflux-, but also alleviate side-effects related to tissue-dependent drug uptake. Finally, we provide an outline of preclinical and clinical studies of nanoparticles formulations for colorectal cancer treatment, and briefly discuss strategies to optimize the selective delivery of these nanomedicines to colorectal cancer cells.