Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme
Abstract Glioblastoma multiforme (GBM) is an incurable aggressive brain cancer in which current treatment strategies have demonstrated limited survival benefit. In recent years, nitrogen-containing bisphosphonates (N-BPs) have demonstrated direct anticancer effects in a number of tumour types includ...
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | Journal of Nanobiotechnology |
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| Online Access: | https://doi.org/10.1186/s12951-021-00856-x |
| _version_ | 1817991107375529984 |
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| author | Lynn N Jena Lindsey A Bennie Emma M McErlean Sreekanth Pentlavalli Kim Glass James F Burrows Vicky L Kett Niamh E Buckley Jonathan A Coulter Nicholas J Dunne Helen O McCarthy |
| author_facet | Lynn N Jena Lindsey A Bennie Emma M McErlean Sreekanth Pentlavalli Kim Glass James F Burrows Vicky L Kett Niamh E Buckley Jonathan A Coulter Nicholas J Dunne Helen O McCarthy |
| author_sort | Lynn N Jena |
| collection | DOAJ |
| description | Abstract Glioblastoma multiforme (GBM) is an incurable aggressive brain cancer in which current treatment strategies have demonstrated limited survival benefit. In recent years, nitrogen-containing bisphosphonates (N-BPs) have demonstrated direct anticancer effects in a number of tumour types including GBM. In this study, a nano-formulation with the RALA peptide was used to complex the N-BP, alendronate (ALN) into nanoparticles (NPs) < 200 nm for optimal endocytic uptake. Fluorescently labelled AlexaFluor®647 Risedronate was used as a fluorescent analogue to visualise the intracellular delivery of N-BPs in both LN229 and T98G GBM cells. RALA NPs were effectively taken up by GBM where a dose-dependent response was evidenced with potentiation factors of 14.96 and 13.4 relative to ALN alone after 72 h in LN229 and T98G cells, respectively. Furthermore, RALA/ALN NPs at the IC50, significantly decreased colony formation, induced apoptosis and slowed spheroid growth in vitro. In addition, H-Ras membrane localisation was significantly reduced in the RALA/ALN groups compared to ALN or controls, indicative of prenylation inhibition. The RALA/ALN NPs were lyophilised to enhance stability without compromising the physiochemical properties necessary for functionality, highlighting the suitability of the NPs for scale-up and in vivo application. Collectively, these data show the significant potential of RALA/ALN NPs as novel therapeutics in the treatment of GBM. |
| first_indexed | 2024-04-14T01:08:45Z |
| format | Article |
| id | doaj.art-ff00e18b61e540388dddf96e6bc47180 |
| institution | Directory Open Access Journal |
| issn | 1477-3155 |
| language | English |
| last_indexed | 2024-04-14T01:08:45Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj.art-ff00e18b61e540388dddf96e6bc471802022-12-22T02:21:09ZengBMCJournal of Nanobiotechnology1477-31552021-05-0119111810.1186/s12951-021-00856-xExploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiformeLynn N Jena0Lindsey A Bennie1Emma M McErlean2Sreekanth Pentlavalli3Kim Glass4James F Burrows5Vicky L Kett6Niamh E Buckley7Jonathan A Coulter8Nicholas J Dunne9Helen O McCarthy10School of Pharmacy, Queen’s University BelfastSchool of Pharmacy, Queen’s University BelfastSchool of Pharmacy, Queen’s University BelfastSchool of Pharmacy, Queen’s University BelfastSchool of Pharmacy, Queen’s University BelfastSchool of Pharmacy, Queen’s University BelfastSchool of Pharmacy, Queen’s University BelfastSchool of Pharmacy, Queen’s University BelfastSchool of Pharmacy, Queen’s University BelfastSchool of Mechanical and Manufacturing Engineering, Dublin City UniversitySchool of Pharmacy, Queen’s University BelfastAbstract Glioblastoma multiforme (GBM) is an incurable aggressive brain cancer in which current treatment strategies have demonstrated limited survival benefit. In recent years, nitrogen-containing bisphosphonates (N-BPs) have demonstrated direct anticancer effects in a number of tumour types including GBM. In this study, a nano-formulation with the RALA peptide was used to complex the N-BP, alendronate (ALN) into nanoparticles (NPs) < 200 nm for optimal endocytic uptake. Fluorescently labelled AlexaFluor®647 Risedronate was used as a fluorescent analogue to visualise the intracellular delivery of N-BPs in both LN229 and T98G GBM cells. RALA NPs were effectively taken up by GBM where a dose-dependent response was evidenced with potentiation factors of 14.96 and 13.4 relative to ALN alone after 72 h in LN229 and T98G cells, respectively. Furthermore, RALA/ALN NPs at the IC50, significantly decreased colony formation, induced apoptosis and slowed spheroid growth in vitro. In addition, H-Ras membrane localisation was significantly reduced in the RALA/ALN groups compared to ALN or controls, indicative of prenylation inhibition. The RALA/ALN NPs were lyophilised to enhance stability without compromising the physiochemical properties necessary for functionality, highlighting the suitability of the NPs for scale-up and in vivo application. Collectively, these data show the significant potential of RALA/ALN NPs as novel therapeutics in the treatment of GBM.https://doi.org/10.1186/s12951-021-00856-xGlioblastoma MultiformeBisphosphonateNanoparticlesAnticancerRALA peptideNanomedicine |
| spellingShingle | Lynn N Jena Lindsey A Bennie Emma M McErlean Sreekanth Pentlavalli Kim Glass James F Burrows Vicky L Kett Niamh E Buckley Jonathan A Coulter Nicholas J Dunne Helen O McCarthy Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme Journal of Nanobiotechnology Glioblastoma Multiforme Bisphosphonate Nanoparticles Anticancer RALA peptide Nanomedicine |
| title | Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme |
| title_full | Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme |
| title_fullStr | Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme |
| title_full_unstemmed | Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme |
| title_short | Exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme |
| title_sort | exploiting the anticancer effects of a nitrogen bisphosphonate nanomedicine for glioblastoma multiforme |
| topic | Glioblastoma Multiforme Bisphosphonate Nanoparticles Anticancer RALA peptide Nanomedicine |
| url | https://doi.org/10.1186/s12951-021-00856-x |
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