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dc.contributor.authorZhou, Jie
dc.contributor.authorMohamed Wali, Aisha Roshan
dc.contributor.authorMa, Shengnan
dc.contributor.authorHe, Yiyan
dc.contributor.authorYue, Dong
dc.contributor.authorTang, James Zhenggui
dc.contributor.authorGu, Zhongwei
dc.date.accessioned2018-07-03T13:12:08Z
dc.date.available2018-07-03T13:12:08Z
dc.date.issued2018-04-24
dc.identifier.citationZhou, J., Mohamed Wali, AR., Ma, S., He, Y., Yue, D., Tang, JZ., Gu, Z. 'Tailoring the Supramolecular Structure of Guanidinylated Pullulan toward Enhanced Genetic Photodynamic Therapy', Biomacromolecules, 19 (6) pp. 2214-2226
dc.identifier.issn1526-4602
dc.identifier.pmid29689167
dc.identifier.doi10.1021/acs.biomac.8b00273
dc.identifier.urihttp://hdl.handle.net/2436/621419
dc.description.abstractIn the progress of designing a gene carrier system, what is urgently needed is a balance of excellent safety and satisfactory efficiency. Herein, a straightforward and versatile synthesis of a cationic guanidine-decorated dendronized pullulan (OGG3P) for efficient genetic photodynamic therapy was proposed. OGG3P was able to block the mobility of DNA from a weight ratio of 2. However, G3P lacking guanidine residues could not block DNA migration until at a weight ratio of 15, revealing guanidination could facilitate DNA condensation via specific guanidinium-phosphate interactions. A zeta potential plateau (∼+23 mV) of OGG3P complexes indicated the nonionic hydrophilic hydroxyl groups in pullulan might neutralize the excessive detrimental cationic charges. There was no obvious cytotoxicity and hemolysis, but also enhancement of transfection efficiency with regard to OGG3P in comparison with that of native G3P in Hela and HEK293T cells. More importantly, we found that the uptake efficiency in Hela cells between OGG3P and G3P complexes was not markedly different. However, guanidination caused changes in uptake pathway and led to macropinocytosis pathway, which may be a crucial reason for improved transfection efficiency. After introducing a therapeutic pKillerRed-mem plasmid, OGG3P complexes achieved significantly enhanced KillerRed protein expression and ROS production under irradiation. ROS-induced cancer cells proliferation suppression was also confirmed. This study highlights the guanidine-decorated dendronized pullulan could emerge as a reliable nonviral gene carrier to specifically deliver therapeutic genes.
dc.formatapplication/PDF
dc.language.isoen
dc.publisherACS Publications
dc.relation.urlhttps://pubs.acs.org/doi/10.1021/acs.biomac.8b00273
dc.subjectDendronised pullulan
dc.subjectguanidination
dc.subjectDNA condensation
dc.subjectcell uptake
dc.subjectcancer cell proliferation suppression
dc.titleTailoring the supramolecular structure of guanidinylated pullulan toward enhanced genetic photodynamic therapy
dc.typeJournal article
dc.identifier.journalBiomacromolecules
dc.date.accepted2018-04-24
rioxxterms.funderGuangdong Natural Science Foundation/ National Science Foundation of China
rioxxterms.identifier.projectUOW03072018JT
rioxxterms.versionAM
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
rioxxterms.licenseref.startdate2018-04-24
dc.source.volume19
dc.source.issue6
dc.source.beginpage2214
dc.source.endpage2226
refterms.dateFCD2018-10-19T09:26:31Z
refterms.versionFCDAM
refterms.dateFOA2018-04-24T00:00:00Z
html.description.abstractIn the progress of designing a gene carrier system, what is urgently needed is a balance of excellent safety and satisfactory efficiency. Herein, a straightforward and versatile synthesis of a cationic guanidine-decorated dendronized pullulan (OGG3P) for efficient genetic photodynamic therapy was proposed. OGG3P was able to block the mobility of DNA from a weight ratio of 2. However, G3P lacking guanidine residues could not block DNA migration until at a weight ratio of 15, revealing guanidination could facilitate DNA condensation via specific guanidinium-phosphate interactions. A zeta potential plateau (∼+23 mV) of OGG3P complexes indicated the nonionic hydrophilic hydroxyl groups in pullulan might neutralize the excessive detrimental cationic charges. There was no obvious cytotoxicity and hemolysis, but also enhancement of transfection efficiency with regard to OGG3P in comparison with that of native G3P in Hela and HEK293T cells. More importantly, we found that the uptake efficiency in Hela cells between OGG3P and G3P complexes was not markedly different. However, guanidination caused changes in uptake pathway and led to macropinocytosis pathway, which may be a crucial reason for improved transfection efficiency. After introducing a therapeutic pKillerRed-mem plasmid, OGG3P complexes achieved significantly enhanced KillerRed protein expression and ROS production under irradiation. ROS-induced cancer cells proliferation suppression was also confirmed. This study highlights the guanidine-decorated dendronized pullulan could emerge as a reliable nonviral gene carrier to specifically deliver therapeutic genes.


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