Journal
ADVANCED DRUG DELIVERY REVIEWS
Volume 63, Issue 8, Pages 659-670Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.addr.2011.02.002
Keywords
Prodrug; Cancer therapy; Targeted delivery; Polymer; Transporter; ADEPT; GDEPT
Categories
Funding
- National Cancer Institute at NIH [1R21CA143683-01]
- National Institute of Alcohol Abuse and Alcoholism at NIH [1R21AA017960-01A1]
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As the mainstay in the treatment of various cancers for several decades, chemotherapy is successful but still faces challenges including non-selectivity and high toxicity. Improving the selectivity is therefore a critical step to improve the therapeutic efficacy of chemotherapy. Prodrug is one of the most promising approaches to increase the selectivity and efficacy of a chemotherapy drug. The classical prodrug approach is to improve the pharmaceutical properties (solubility, stability, permeability, irritation, distribution, etc.) via a simple chemical modification. This review will focus on various targeted prodrug designs that have been developed to increase the selectivity of chemotherapy drugs. Various tumor-targeting ligands, transporter-associated ligands, and polymers can be incorporated in a prodrug to enhance the tumor uptake. Prodrugs can also be activated by enzymes that are specifically expressed at a higher level in tumors, leading to a selective antitumor effect. This can be achieved by conjugating the enzyme to a tumor-specific antibody, or delivering a vector expressing the enzyme into tumor cells. (C) 2011 Elsevier B.V. All rights reserved.
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