title: Multifunctional QD-based co-delivery of siRNA and doxorubicin to HeLa cells for reversal of multidrug resistance and real-time tracking.
abstract: Co-delivery of siRNA and chemotherapeutic agents has been developed to combat multidrug resistance in cancer therapy. Recently, we developed a series of quantum dots (QDs) functionalized by β-cyclodextrin (β-CD) coupled to amino acids, some of which can be used to facilitate the delivery of siRNA. In this study, two CdSe/ZnSe QDs modified with β-CD coupled to L-Arg or L-His were used to simultaneously deliver doxorubicin (Dox) and siRNA targeting the MDR1 gene to reverse the multidrug resistance of HeLa cells. In this co-delivery system, Dox was firstly encapsulated into the hydrophobic cavities of β-CD, resulting in bypass of P-glycoprotein (P-gp)-mediated drug efflux. After complex formation of the mdr1 siRNA with Dox-loaded QDs via electrostatic interaction, significant down-regulation of mdr1 mRNA levels and P-gp expression was achieved as shown by RT-PCR and Western blotting experiments, respectively. The number of apoptotic HeLa cells after treatment with the complexes substantially exceeded the number of apoptotic cells induced by free Dox only. The intrinsic fluorescence of the QDs provided an approach to track the system by laser confocal microscopy. These multifunctional QDs are promising vehicles for the co-delivery of nucleic acids and chemotherapeutics and for real-time tracking of treatment.
authors.affiliation: MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
authors.forename: Jin-Ming
authors.initials: JM
authors.lastname: Li
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Wang
authors.forename: Mei-Xia
authors.initials: MX
authors.lastname: Zhao
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Tan
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Li
authors.forename: Xue-Yi
authors.initials: XY
authors.lastname: Le
authors.forename: Liang-Nian
authors.initials: LN
authors.lastname: Ji
authors.forename: Zong-Wan
authors.initials: ZW
authors.lastname: Mao
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000327:Adsorption / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D058948:Cell Tracking / Q000379:methods*; D004317:Doxorubicin / Q000494:pharmacology*; D016503:Drug Delivery Systems / Q000379:methods*; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D045663:Quantum Dots; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D055672:Static Electricity; D013997:Time Factors
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D034741:RNA, Small Interfering; D004317:Doxorubicin