We have previously reported the development of a versatile nanocarrier platform comprised of PEG-cholic acid cluster telodendrimers that can self-assemble together with hydrophobic cytotoxic anti-cancer agents to form stable nanoparticle drugs. We have successfully loaded these nanoparticles with a number of different cancer drugs. These include paclitaxel, doxorubicin, vincristine, vinblastine, actinomycin D, bortezomib, temsirolimus, sarofinib, and lapatinib. Using electron paramagnetic resonance spectroscopy, we have demonstrated that the micelles can be disrupted by LDL and VLDL causing premature drug release. Such undesirable properties can be eliminated by cross-linking the telodendrimers with disulfide bonds. The disulfide crosslinked micelles can be triggered to release drugs by endogenous glutathione inside the cancer cells or via exogenous addition of N-acetyl cysteine, a FDA approved-drug that has been used for years in the treatment of Tylenol overdose. Very recently, we created a novel crosslinking strategy by incorporating boronic acids or catechols into the telodendrimers. The final nanocarriers were crosslinked by boronate-catechol bonds resulting in stable micelles, thus avoiding premature drug release. Inside the endosomal compartment, the boronate-catechol bonds were cleaved by the acidic environment resulting in drug release. An additional very important feature of this nanocarrier is that exogenous mannitol (another FDA-approved drug for diuresis) can be administered in vivo to trigger drug release. Therapeutic studies in ovarian cancer xenograft model indicated that paclitaxel-loaded boronate-catechol crosslinked nanoparticles were much more efficacious when mannitol was given 24 hours after each dose of nanoparticle drug.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1943. doi:1538-7445.AM2012-1943