ABSTRACT
Codelivery of chemotherapeutics via nanomaterials has attracted much attention over the last decades due to improved drug delivery to tumor tissues, decreased systemic effects, and increased therapeutic efficacies. High porosities, large pore volumes and surface areas, and tunable structures have positioned metal-organic frameworks (MOFs) as promising drug delivery systems (DDSs). In particular, nanoscale Zr-linked MOFs such as MOF-808 offer notable advantages for biomedical applications such as high porosity, good stability, and biocompatibility. In this study, we report efficient dual drug delivery of floxuridine (FUDR) and carboplatin (CARB) loaded in MOF-808 nanoparticles to cancer cells. The nanoparticles were further functionalized by a poly(acrylic acid-mannose acrylamide) (PAAMAM) glycopolymer coating to obtain a highly selective DDS in cancer cells and enhance the therapeutic efficacy of chemotherapy. While MOF-808 was found to enhance the individual therapeutic effects of FUDR and CARB toward cancerous cells, combining FUDR and CARB was seen to cause a synergistic effect, further enhancing the cytotoxicity of the free drugs. Enhancement of CARB loading and therefore cytotoxicity of the CARB-loaded MOFs could be induced through a modified activation protocol, while coating of MOF-808 with the PAAMAM glycopolymer increased the uptake of the nanoparticles in cancer cells used in the study and offered a particularly significant selective drug delivery with high cytotoxicity in HepG2 human hepatocellular carcinoma cells. These results show how the enhancement of cytotoxicity is possible through both nanovector delivery and synergistic treatment, and that MOF-808 is a viable candidate for future drug delivery studies.
ABSTRACT
The use of nanomaterials in biomedicine has increased over the past 10 years, with many different nanoparticle systems being utilised within the clinical setting. With limited emerging success in clinical trials, polymeric, metallic, and lipid based nanoparticles have all found a place in medicine, with these generally providing enhanced drug efficacy or therapeutic effect compared to the standard drug treatments. Although there is great anticipation surrounding the field of nanomedicine and its influence on the pharmaceutical industry, there is currently very little regulatory guidance in this area, despite repeated calls from the research community, something that is critical to provide legal certainty to manufacturers, policymakers, healthcare providers and the general public. This is reflected in the lack of an international definition of what these materials are, with several bodies, including the National Institute of Health, USA, the European Science Foundation and the European Technology Platform, having differing definitions, and the FDA having no clear definition at all. The uncertainty created by the lack of consistency across the board may ultimately impact funding, research and development of such products negatively thus destroying public acceptance and perception of nano-products. This review aims to discuss the use of nanomaterials within the clinical setting, why regulation of these materials is so important, and the challenges faced in regulating these materials generally, as well as the current regulation used in different nations.
