Inhibition of protein-protein interactions using biodegradable depsipeptide nanoassemblies.

Although peptides notoriously have poor intrinsic pharmacokinetic properties, it is well-known that nanostructures with excellent pharmacokinetic properties can be designed. Noticing that peptide inhibitors are generally nonpolar, here, we consolidate the peptide inhibitor targeting intracellular protein-protein interactions (PPIs) as an integral part of biodegradable self-assembled depsipeptide nanostructures (SdPNs). Because the peptide inhibitor has the dual role of PPI inhibition and self-assembly in this design, problems associated with the poor pharmacokinetics of peptides and encapsulation/entrapment processes can be overcome. Optimized SdPNs displayed better tumor targeting and PPI inhibition properties than the comparable small molecule inhibitor in vivo. Kinetics of PPI inhibition for SdPNs were gradual and controllable in contrast to the rapid inhibition kinetics of the small molecule. Because SdPN is modular, any appropriate peptide inhibitor can be incorporated into the platform without concern for the poor pharmacokinetic properties of the peptide.

Perfluorooctylbromide-loaded fucoidan-chlorin e6 nanoparticles for tumor-targeted photodynamic therapy.

Efficient delivery of a photosensitizer (PS) and oxygen to tumor tissue is critical for successful photodynamic therapy (PDT). For this purpose, we developed a fucoidan (Fu)-chlorin e6 (Ce6) nanoparticle (NP) containing perfluorooctylbromide (PFOB). Fu, a biopolymer derived from seaweed, made up the hydrophilic shell of the NP and provided specific targeting to tumor cells by P-selectin binding. Conjugation with the hydrophobic Ce6 enabled self-assembly and Ce6-generated cytotoxic reactive oxygen species to kill tumor cells upon laser irradiation. PF supplied oxygen to the hypoxic tumor tissue and increased the efficacy of the PDT. The developed Fu-Ce6-PF-NPs bound specifically to SCC7 tumor cells and killed them via a photodynamic effect on laser irradiation. High accumulation of the NPs in tumor tissue and improved tumor suppression by PDT were observed in SCC7 tumor-bearing mice. The overall data demonstrated the potential of Fu-Ce6-PF-NP as a tumor-targeting drug carrier for effective PDT.

Rhamnolipid-coated W/O/W double emulsion nanoparticles for efficient delivery of doxorubicin/erlotinib and combination chemotherapy.

BACKGROUND: Combination therapy using more than one drug can result in a synergetic effect in clinical treatment of cancer. For this, it is important to develop an efficient drug delivery system that can contain multiple drugs and provide high accumulation in tumor tissue. In particular, simultaneous and stable loading of drugs with different chemical properties into a single nanoparticle carrier is a difficult problem. RESULTS: We developed rhamnolipid-coated double emulsion nanoparticles containing doxorubicin and erlotinib (RL-NP-DOX-ERL) for efficient drug delivery to tumor tissue and combination chemotherapy. The double emulsion method enabled simultaneous loading of hydrophilic DOX and hydrophobic ERL in the NPs, and biosurfactant RL provided stable surface coating. The resulting NPs showed fast cellular uptake and synergetic tumor cell killing in SCC7 cells. In real-time imaging, they showed high accumulation in SCC7 tumor tissue in mice after intravenous injection. Furthermore, enhanced tumor suppression was observed by RL-NP-DOX-ERL in the same mouse model compared to control groups using free drugs and NPs containing a single drug. CONCLUSIONS: The developed RL-NP-DOX-ERL provided efficient delivery of DOX and ERL to tumor tissue and successful tumor therapy with a synergetic effect. Importantly, this study demonstrated the promising potential of double-emulsion NPs and RL coating for combination therapy.