DNA Block Copolymer Micelles - highly modular system for chemotherapeutic and nucleic acid drug delivery offered by Max Planck Institute for Polymer Research
The greatest challenge in drug targeting is to achieve higher organ or tissue selectivity. Another so far unsolved problem is the delivery of nucleic acid drugs.
Most of the available anti-cancer agents are not able to differ between healthy and cancerous cells and thus lead to systemic toxicity. The basic idea for the solution of this problem is the application of polymeric nanoparticles equipped with targeting units for tumor-specific delivery. For instance amphiphilic block copolymers, which self-assemble in dilute aqueous solutions into three-dimensional spherical micelles with a hydrophilic corona and a hydrophobic core are an attractive option. These nanosized particles with a typical size of 10-100 nm are able to accommodate lipophilic drugs in their interior and alter their kinetics in vitro and in vivo. The new type of amphiphilic block copolymers are build up of a hydrophobic synthetic polymer component in the core and single-stranded DNA forming the corona of these micelles.
As new targets for specific localization of chemotherapeutics incorporated into nanoparticle folate receptors (FRs) are considered because they are highly expressed on the surface of various cancer cells.
Scientists from the Max Planck Institute for Polymer Research in Mainz introduced DNA block copolymer micelles as a highly modular system for chemotherapeutic and nucleic acid drug delivery. These micelles are composed of oligodeoxynucleotide-modified targeting units fixed into the micelle corona by hybridization, allowing perfect control of surface functionalities of the nanoparticle system. The interior of the micelles consisting of polypropylene oxide (PPO) was loaded efficiently with the hydrophobic anticancer drug Doxorubicin (Dox).
It could be shown that the uptake of these DNA block copolymer micelles depends on the density and position of the folate (FA). The higher the number of FA entities at the rim, the more efficiently the nanoparticles are internalized. Targeting units hidden inside the nanoparticles could not be recognized by the folate receptors, indicating that the micelles remain intact and do not dissociate into isolated block copolymers.
Furthermore, the internalization of Dox-loaded micelles in the cancerous cell line, human colon adenocarcinoma (Caco-2), resulted in efficient cytotoxity and high mortality and thus indicates aligned drug delivery into the tumor cells. The striking advantage of this novel drug delivery vehicles is the ease of generating multifunctional nano-objects. The functionality of choice just needs to be coupled to oligonucleotides and can then be hybridized to the micelles. In addition to equipping the nanoparticles with only targeting and drug units other features like stealth functions, hydrophilic drugs and diagnostic agents could be introduced as well.
EP and PCT application filed
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