Effective combination treatment of lung cancer cells by single vehicular delivery of siRNA and different anticancer drugs.
In recent years, lung cancer has become one of the fastest growing cancers in the world. Thus, the development of efficient combination therapy to treat lung cancer has attracted significant attention in the cancer therapy field. In this article, we developed a single vehicle drug delivery system, based on quantum dot (QD) nanoparticles, to deliver small interfering RNA (siRNA; target Bcl-2) and different anticancer drugs (carboplatin, paclitaxel, and doxorubicin) simultaneously for treating A549 lung cancer cells efficiently by combination therapy. The QD nanoparticles were conjugated with l-arginine (l-Arg) and different kinds of hydroxypropyl-cyclodextrins (HP-α-CDs, HP-β-CDs, and HP-γ-CDs) on the surface to form the delivery nanocarriers (QD nanocarriers). They were able to not only bind and transport the siRNA through electrostatic interactions with l-Arg residues but also accommodate various disparate anticancer drugs using different HP-CD modifications. Compared with free drug treatments, the use of QD nanocarriers to deliver Bcl-2 siRNA and different anticancer drugs simultaneously exerted a threefold to fourfold increase in cytotoxicity in A549 cells, which greatly improved the treatment efficacy through combined action. Furthermore, the QD nanocarriers could be used as a probe for real-time imaging of the drug delivery and release because of their strong fluorescence properties. These findings indicate that multifunctional QD nanocarriers hold great promise as a powerful tool for combination therapy for lung cancer.
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
Jinming
J
Li
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
Yuanyuan
Y
Wang
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
Shanshan
S
Xue
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
Jinghua
J
Sun
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
Wei
W
Zhang
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
Ping
P
Hu
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
Liangnian
L
Ji
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, People's Republic of China.
Zongwan
Z
Mao
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001120:Arginine / Q000737:chemistry; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004705:Endocytosis / Q000187:drug effects; D005434:Flow Cytometry; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008024:Ligands; D008175:Lung Neoplasms / Q000188:drug therapy*; D053758:Nanoparticles / Q000737:chemistry; D017239:Paclitaxel / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D045663:Quantum Dots / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D047392:beta-Cyclodextrins / Q000138:chemical synthesis / Q000737:chemistry
D000970:Antineoplastic Agents; D004337:Drug Carriers; D008024:Ligands; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D004317:Doxorubicin; D001120:Arginine; D017239:Paclitaxel
Bcl-2 siRNA; anticancer drugs; combination therapy; lung cancer cells; quantum dot nanocarriers
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