Prodrug Applications for Targeted Cancer Therapy
Journal Title: The AAPS Journal - Year 2014, Vol 16, Issue 5
Abstract
Prodrugs are widely used in the targeted delivery of cytotoxic compounds to cancer cells. To date, targeted prodrugs for cancer therapy have achieved great diversity in terms of target selection, activation chemistry, as well as size and physicochemical nature of the prodrug. Macromolecular prodrugs such as antibody-drug conjugates, targeted polymer-drug conjugates and other conjugates that self-assemble to form liposomal and micellar nanoparticles currently represent a major trend in prodrug development for cancer therapy. In this review, we explore a unified view of cancer-targeted prodrugs and highlight several examples from recombinant technology that exemplify the prodrug concept but are not identified as such. Recombinant “prodrugs” such as engineered anthrax toxin show promise in biological specificity through the conditionally targeting of multiple cellular markers. Conditional targeting is achieved by structural complementation, the spontaneous assembly of engineered inactive subunits or fragments to reconstitute functional activity. These complementing systems can be readily adapted to achieve conditionally bispecific targeting of enzymes that are used to activate low-molecular weight prodrugs. By leveraging strengths from medicinal chemistry, polymer science, and recombinant technology, prodrugs are poised to remain a core component of highly focused and tailored strategies aimed at conditionally attacking complex molecular phenotypes in clinically relevant cancer.
Authors and Affiliations
Irene Giang, Erin L. Boland, Gregory M. K. Poon
Keywords
Related Articles
- EP ID EP681659
- DOI 10.1208/s12248-014-9638-z
- Views 65
- Downloads 0
Light-scattering investigations on dilute nonionic oil-in-water microemulsions
Dilute 3-component nonionic oil-in-water microemulsions formulated with either a polyoxyethylene surfactant (C18∶1E10 or C12E10) or the alkylamine-N-oxide surfactant, DDAO (C12AO), and containing either a triglyc...
Epigenetic Modifications of Nrf2 by 3,3′-diindolylmethane In Vitro in TRAMP C1 Cell Line and In Vivo TRAMP Prostate Tumors
The online version of this article (doi:10.1208/s12248-013-9493-3) contains supplementary material, which is available to authorized users.
Molecular Mechanisms of Silibinin-Mediated Cancer Chemoprevention with Major Emphasis on Prostate Cancer
Despite advances in early detection, prostate cancer remains the second highest cancer mortality in American men, and even successful interventions are associated with enormous health care costs as well as prolonged dele...
Influence of Surface Chemistry on Cytotoxicity and Cellular Uptake of Nanocapsules in Breast Cancer and Phagocytic Cells
The online version of this article (doi:10.1208/s12248-014-9572-0) contains supplementary material, which is available to authorized users.
Development and evaluation of a population pharmacokinetic-pharmacodynamic model of darbepoetin alfa in patients with nonmyeloid malignancies undergoing multicycle chemotherapy
Anemia is frequently observed in patients undergoing chemotherapy. Administration of darbepoetin alfa, a recombinant erythropoiesis-stimulating agent that has longer residence time than endogenous erythropoietin, to pati...