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dc.contributor.authorAl-Jamal, Khuloud
dc.contributor.authorAl-Jamal, Wafa
dc.contributor.authorWang, Julie T.-W.
dc.contributor.authorRubio, Noelia
dc.contributor.authorBuddle, Joanna
dc.contributor.authorGathercole, David
dc.contributor.authorZloh, Mire
dc.contributor.authorKostarelos, Kostas
dc.identifier.citationAl-Jamal , K , Al-Jamal , W , Wang , J T-W , Rubio , N , Buddle , J , Gathercole , D , Zloh , M & Kostarelos , K 2013 , ' Cationic Poly-l-lysine Dendrimer Complexes Doxorubicin and Delays Tumor Growth in Vitro and in Vivo ' , ACS Nano , vol. 7 , no. 3 , pp. 1905-17 .
dc.identifier.otherPURE: 1576612
dc.identifier.otherPURE UUID: d6810386-d94c-496f-ac25-8d6da1bca00e
dc.identifier.otherScopus: 84875656722
dc.description.abstractWe report in this study the complexation of the chemotherapeutic drug doxorubicin (DOX) with the novel sixth-generation cationic poly-l-lysine dendrimer (DM) (MW 8149 kDa), which we previously reported to exhibit systemic antiangiogenic activity in tumor-bearing mice. DOX–DM complexation was confirmed by florescence polarization measurement, proton nuclear magnetic resonance spectroscopy, and molecular modeling. Enhanced penetration of DOX–DM (at 1:10 molar ratio), compared to the free DOX, into prostate 3D multicellular tumor spheroids (MTS) was confirmed by confocal laser scanning microscopy. Furthermore, DOX–DM complexes achieved a significantly higher cytotoxicity in DU145 MTS system compared to the free drug, as shown by growth delay curves. Incubation of MTS with low DOX concentration (1 μM) complexed with DM led to a significant delay in MTS growth compared to untreated MTS or MTS treated with free DOX. DOX–DM complex retention was also achieved in a Calu-6 lung cancer xenograft model in tumor-bearing mice, as shown by live whole animal fluorescence imaging. Therapeutic experiments in B16F10 tumor bearing mice have shown enhanced therapeutic efficacy of DOX when complexed to DM. This study suggests that the cationic poly-l-lysine DM molecules studied here could, in addition to their systemic antiangiogenic property, complex chemotherapeutic drugs such as DOX and improve their accumulation and cytotoxicity into MTS and solid tumors in vivo. Such an approach offers new capabilities for the design of combinatory antiangiogenic/anticancer therapeutics.en
dc.relation.ispartofACS Nano
dc.subjectcancer; growth delay; penetration; uptake; retention; fluorescence; solid tumor
dc.titleCationic Poly-l-lysine Dendrimer Complexes Doxorubicin and Delays Tumor Growth in Vitro and in Vivoen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionDepartment of Pharmacy
dc.contributor.institutionMedicinal and Analytical Chemistry
dc.description.statusPeer reviewed
rioxxterms.typeJournal Article/Review

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