A new and selective breast cancer-targeting prodrug system is described based on the Staudinger ligation bioorthogonal reaction.

The genomic revolution has identified therapeutic targets for a plethora of diseases, creating a need to develop robust technologies for combination drug therapy. In the present work, we describe a self-assembled polymeric nanoparticle (NP) platform to target and control precisely the codelivery of drugs with varying physicochemical properties to cancer cells. As proof of concept, we codelivere...

BACKGROUND: Antibody-directed enzyme prodrug therapy (ADEPT) is a promising new approach to deliver anticancer drugs selectively to tumor cells. In this approach, an enzyme is conjugated to a tumor-specific antibody. The antibody selectively localizes the enzyme to the tumor cell surface. Subsequent administration of a prodrug substrate of the enzyme leads to the enzyme-catalyzed release of the...

We examined the concept of a novel prodrug strategy in which anticancer drug can be locally released by visible/near IR light, taking advantage of the photodynamic process and photo-unclick chemistry. Our most recently formulated prodrug of combretastatin A-4, Pc-(L-CA4)2, showed multifunctionality for fluorescence imaging, light-activated drug release, and the combined effects of PDT and local...

Metronidazole (MTDZ), the drug of choice for the treatment of protozoal infections such as luminal amebiasis, is highly susceptible to colonic metabolism, which may hinder its conversion from a colon-specific prodrug to an effective anti-amebic agent targeting the entire large intestine. Thus, in an attempt to control the colonic distribution of the drug, a polymeric colon-specific prodrug, MTD...

Absorption and lymphatic transfer of a polymeric prodrug of mitomycin C (MMC), mitomycin C-dextran conjugate (MMC-D), following i.m. injection were studied in rats in order to assess the feasibility of a macromolecular prodrug as a lymphotropic delivery system. Three types of MMC-D, conjugates with dextran with molecular weights of 10,000, 70,000 and 500,000, were synthesized, and the dispositi...

The peptidyl prodrug (1S,2S,5R,6S)-2-[(2'S)-(2-Amino)propionyl]a-minobicyclo[3.1.0.]hexen-2,6-dicarboxylic acid, also known as LY544344, was discovered to improve the oral bioavailability of the parent drug (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740), a potent group II metabotropic glutamate receptor agonist. This prodrug has been shown to deliver high plasma concentrations...

Intoroduction Prodrug approach deals with chemical biotransformation or enzymatic conversion or involves inactive or less active bio-reversible derivatives of active drug molecules. They have to pass through enzymatic or chemical biotransformation before eliciting their pharmacological action. Methods & Materials The two different pharmacophores combine to give synergistic activity or may hel...

In antibody-directed enzyme prodrug therapy, an enzyme conjugated to an antitumor antibody is given i.v. and localizes in the tumor. A prodrug is then given, which is converted to a cytotoxic drug selectively in the tumor. Ten patients with colorectal carcinoma expressing carcinoembryonic antigen received antibody-directed enzyme prodrug therapy with A5B7 F(ab*)2 antibody to carcinoembryonic an...

DFT calculation results for intramolecular proton transfer reactions in Kirby's enzyme models 1-7 reveal that the reaction rate is quite responsive to geometric disposition, especially to distance between the two reactive centers, r (GM), and the angle of attack, α (the hydrogen bonding angle). Hence, the study on the systems reported herein could provide a good basis for designing aza nucleosi...