Overcoming Drug Resistance in Colon Cancer by Aptamer-Mediated Targeted Co-Delivery of Drug and siRNA Using Grapefruit-Derived Nanovectors
| Autor: | Mingyue Tao, Wei-Jie Dai, Mengchu Yao, Qilong Wang, Yali Jun, Xiaofei Chen, Baofei Jiang, Li Zhang, Zhuang Tang, Wei Yan, Yong Gao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cancer therapy Aptamer Physiology Grapefruit-derived nanovectors media_common.quotation_subject Down-Regulation Antineoplastic Agents Mice SCID 02 engineering and technology Multidrug resistance lcsh:Physiology Flow cytometry lcsh:Biochemistry Mice 03 medical and health sciences Downregulation and upregulation In vivo Cell Line Tumor medicine Animals Humans Tissue Distribution Doxorubicin lcsh:QD415-436 ATP Binding Cassette Transporter Subfamily B Member 1 RNA Small Interfering Internalization media_common Drug Carriers Mice Inbred BALB C medicine.diagnostic_test lcsh:QP1-981 Chemistry Aptamers Nucleotide 021001 nanoscience & nanotechnology Nanostructures Multiple drug resistance 030104 developmental biology Drug Resistance Neoplasm Colonic Neoplasms Drug delivery Cancer cell Cancer research 0210 nano-technology Citrus paradisi medicine.drug |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 50, Iss 1, Pp 79-91 (2018) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: Multidrug resistance (MDR) is the most common cause of chemotherapy failure. Upregulation of P-glycoprotein (P-gp) is one of the main mechanisms underlying MDR. Methods: In this study, we developed a targeted drug and small interfering (si)RNA co-delivery system based on specific aptamer-conjugated grapefruit-derived nanovectors (GNVs) that we tested in MDR LoVo colon cancer cells. The internalization of nanovectors in cancer cells was tested by fluorescence microscopy and flow cytometry. The anti-cancer activity in vitro was determined by colony formation and cell apoptosis assays. The biodistribution of nanovectors was analyzed by live imaging and the anti-cancer activity in vivo was observed. Results: GNVs loaded with aptamer increased doxorubicin (Dox) accumulation in MDR LoVo cells, an effect that was abolished by pretreatment with DNase. The LA1 aptamer effectively promoted nanovector internalization into cells at 4°C and increased the targeted delivery of Dox to tumors. Constructs harboring Dox, LA1, and P-gp siRNA more effectively inhibited proliferation and enhanced apoptosis in cultured MDR LoVo cells while exhibiting more potent anti-tumor activity in vivo than free Dox or GNVs loaded with Dox alone or in conjunction with LA1, an effect that was associated with downregulation of P-gp expression. Conclusion: This GNV-based system may be an effective strategy for overcoming MDR in clinical settings. |
| Databáze: | OpenAIRE |
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