Abstract
Extensive research over the last decade has resulted in a number of highly potent tubulin polymerization inhibitors acting either as microtubule stabilizing agents (MSAs) or microtubule destabilizing agents (MDAs). These inhibitors have potent cytotoxicity against a broad spectrum of human tumor cell lines. In addition to cytotoxicity, a number of these tubulin inhibitors have exhibited abilities to inhibit formation of new blood vessels as well as disrupt existing blood vessels. Tubulin inhibitors as a vascular disrupting agents (VDAs), mainly from the MDA family, induce rapid tumor vessel occlusion and massive tumor necrosis. Thus, tubulin inhibitors have become increasingly popular in the field of tumor vasculature. However, their pharmaceutical application is halted by a number of limitations including poor solubility and toxicity. Thus, recently, there has been considerable interests in the nanoparticle drug delivery of tubulin inhibitors to circumvent those limitations. This article reviews recent advances in nanoparticle based drug delivery for tubulin inhibitors as well as their tumor vasculature disruption properties.
Highlights
Since the discovery of the action of colchicine by Borisy et al [1] in 1967, for the last 50 years, tubulin/microtubules have been long thought to be crucial chemotherapy targets in various cancer types, especially for breast, lung, ovarian and pancreatic carcinomas [2]
Microtubule-targeting agents can be divided into two main separated groups depending on their mechanisms of actions, microtubule-stabilizing (MSA) and microtubule destabilizing agents (MDA) [7]
microtubule stabilizing agents (MSAs) prefers to bind to the polymerized tubulins and stabilize microtubules, while MDAs prefer to bind to the tubulin dimers and destabilize microtubules [8,9]
Summary
Since the discovery of the action of colchicine by Borisy et al [1] in 1967, for the last 50 years, tubulin/microtubules have been long thought to be crucial chemotherapy targets in various cancer types, especially for breast, lung, ovarian and pancreatic carcinomas [2]. 2. For last few decades after a discovery tubulin many inhibitors of MSAs and/or MDAs been for few clinical activity to treat aggressive tumors based with α-subunit as summarized inhave. MDAs have beendrugs usedcan foract clinical activity to treat agents [14,15], rapidly depolymerizing microtubules of of newly formed to shut down the aggressive tumors based on their unique mechanisms action. To overcome the barrier properties of currentofinconvenient for its followed our previous review about overview of colchicine binding agents [18], this review provides treatment, a variety of studies have focused on improving the pharmaceutical properties of their an As overview of itsour nanoparticle delivery angiogenesis of those binding microtubule-targeting drugs agents. Recently,Delivery a numberof ofTubulin research groups both from academia and industry have come up with a
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