Abstract
The use of platinum-based chemotherapeutic drugs in cancer therapy still suffers from severe disadvantages, such as lack of appropriate selectivity for tumor tissues and insurgence of multi-drug resistance. Moreover, drug efficacy can be attenuated by several mechanisms such as premature drug inactivation, reduced drug uptake inside cells and increased drug efflux once internalized. The use of functionalized carbon nanotubes (CNTs) as chemotherapeutic drug delivery systems is a promising strategy to overcome such limitations due to their ability to enhance cellular internalization of poorly permeable drugs and thus increase the drug bioavailability at the diseased site, compared to the free drug. Furthermore, the possibility to encapsulate agents in the nanotubes' inner cavity can protect the drug from early inactivation and their external functionalizable surface is useful for selective targeting. In this study, a hydrophobic platinum(IV) complex was encapsulated within the inner space of two different diameter functionalized multi-walled CNTs (Pt(IV)@CNTs). The behavior of the complexes, compared to the free drug, was investigated on both HeLa human cancer cells and RAW 264.7 murine macrophages. Both CNT samples efficiently induced cell death in HeLa cancer cells 72 hours after the end of exposure to CNTs. Although the larger diameter CNTs were more cytotoxic on HeLa cells compared to both the free drug and the smaller diameter nanotubes, the latter allowed a prolonged release of the encapsulated drug, thus increasing its anticancer efficacy. In contrast, both Pt(IV)@CNT constructs were poorly cytotoxic on macrophages and induced negligible cell activation and no pro-inflammatory cytokine production. Both CNT samples were efficiently internalized by the two types of cells, as demonstrated by transmission electron microscopy observations and flow cytometry analysis. Finally, the platinum levels found in the cells after Pt(IV)@CNT exposure demonstrate that they can promote drug accumulation inside cells in comparison with treatment with the free complex. To conclude, our study shows that CNTs are promising nanocarriers to improve the accumulation of a chemotherapeutic drug and its slow release inside tumor cells, by tuning the CNT diameter, without inducing a high inflammatory response.
Highlights
Chemotherapy, either alone or in combination with surgery and radiation therapy, is widely used to treat different types of cancer
Two types of multi-walled CNTs (MWCNTs) with different diameters and length distributions were used in this study
We used non-commercial MWCNTs (L-carbon nanotubes (CNTs)) with a bigger external diameter (38 nm in average, n = 144, σ = 13.6) and a length ranging from 200 nm to several microns
Summary
Nanoscale ovarian and non-small-cell lung cancer.[2]. Pt(IV) complexes have been synthesized as inactive cisplatin prodrugs, which can be converted to their active Pt(II) form upon cleavage of the axial ligands.[3]. CNTs are among the most attractive nanovectors under investigation.[12] Functionalized CNTs ( f-CNTs) have shown great promise as tools for biomedical applications This is due to their well demonstrated ability to cross biological barriers entering and accumulating inside cells.[13,14] In addition, their high surface area provides multiple attachment sites for molecules and are in turn useful for selective targeting.[15] CNTs have been used as biosensors, as scaffolds for regenerative medicine and as delivery systems of many bioactive molecules, including various anti-cancer agents.[16,17,18,19] Therapeutic molecules can be either attached on the external CNT wall or encapsulated within their inner cavity, protecting the drug from premature inactivation and enabling the possibility of controlled drug release.[20] On the other hand, different approaches have been developed to make this material biocompatible and recently, it has been demonstrated that f-CNTs can be degraded by oxidative enzymes.[21]. The effect of the MWCNT diameter on the release and activity of the Pt(IV) prodrug was examined for the first time
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
