Development of Self-Assembled Biomimetic Boc-Protected Peptide-Polymer Based Nanovehicles for Targeted Delivery to Tumor Cells
Although effective, chemotherapeutic drugs often cause undesired side-effects. Thus, encapsulating chemotherapeutic drugs into nanoscale drug delivery vehicles (DDVs) has the potential to reduce side effects and promote targeted delivery. By mimicking ABA like block-co-polymer systems, we have developed a new amphiphilic biomimetic co-polymer Boc-Ile-PEG-Ile-Boc which was found to readily self-assemble into nanomicelles within hydrophilic shell structures. To facilitate targeting tumor cells, the nanoassemblies were bound to folate, leading to the formation of core shell like structures (IBP-F). Gold nanoparticles (AuNPs), were then embedded followed by functionalization with a second layer of folate. The final DDV system abbreviated (IBP-F-Au-F) formed a multi-layered nanostructure that was capable of efficiently encapsulating the anti-tumor drug tamoxifen. For comparison, we also examined the efficacy of the IBP-F assemblies as DDVs in the absence of AuNPs and a second folate layer. Release profiles showed an initial burst release, followed by sustained release. The DDVs were found to be biocompatible. Upon encapsulating the DDVs with tamoxifen, cell proliferation was inhibited over a period of 72 hours for both DDVs, while non-cancerous dermal fibroblasts continued to proliferate, thus indicating specific targeting ability of the DDVs. Confocal microscopy studies conducted in the presence of human breast cancer cells, MDA-MDB 231 revealed that the drug loaded assemblies were successfully internalized within the cells. SPR analysis demonstrate that IBP-F-Au-F had a higher affinity for breast cancer cells over non-cancerous keratinocyte cells. Thus, we have developed a new family of DDVs that selectively targets tumor cells.
A. M. Brown et al., "Development of Self-Assembled Biomimetic Boc-Protected Peptide-Polymer Based Nanovehicles for Targeted Delivery to Tumor Cells", Journal of Biomimetics, Biomaterials and Biomedical Engineering, Vol. 29, pp. 33-53, 2016