PMID- 30584299 OWN - NLM STAT- MEDLINE DCOM- 20190204 LR - 20231004 IS - 1178-2013 (Electronic) IS - 1176-9114 (Print) IS - 1176-9114 (Linking) VI - 13 DP - 2018 TI - Bacterial magnetosomes-based nanocarriers for co-delivery of cancer therapeutics in vitro. PG - 8269-8279 LID - 10.2147/IJN.S180503 [doi] AB - In recent times, co-delivery of therapeutics has emerged as a promising strategy for treating dreadful diseases such as cancer. MATERIALS AND METHODS: In this study, we developed a novel nanocarrier based on bacterial magnetosomes (BMs) that co-loaded with siRNA and doxorubicin (DOX) using polyethyleneimine (PEI) as a cross-linker (BMs/DP/siRNA). The delivery efficiency of siRNA as well as the pH-responsive release of DOX, and synergistic efficacy of these therapeutics in vitro were systematically investigated. RESULTS: The structure of DOX-PEI (DP) conjugates that synthesized via hydrazone bond formation was confirmed by 1H nuclear magnetic resonance (NMR). The in vitro release experiments showed that the DP conjugate (DOX-loading efficiency - 5.77%+/-0.08%) exhibited the long-term release behavior. Furthermore, the optimal BMs/DP/siRNA particle size of 107.2 nm and the zeta potential value of 31.1+/-1.0 mV facilitated enhanced cellular internalization efficiency. Moreover, the agarose gel electrophoresis showed that the co-delivery system could protect siRNA from degradation in serum and RNase A. In addition, the cytotoxicity assay showed that BMs/DP/siRNA could achieve an excellent synergistic effect compared to that of siRNA delivery alone. The acridine orange (AO)/ethidium bromide (EB) double staining assay also showed that BMs/DP/siRNA complex could induce cells in a stage of late apoptosis and nanocomplex located in the proximity of the nucleus. CONCLUSION: The combination of gene and chemotherapeutic drug using BMs is highly efficient, and the BMs/DP/siRNA would be a promising therapeutic strategy for the future therapeutics. FAU - Long, Rui-Min AU - Long RM AD - College of Chemical Engineering, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. AD - Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. FAU - Dai, Qing-Lei AU - Dai QL AD - College of Chemical Engineering, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. FAU - Zhou, Xia AU - Zhou X AD - College of Chemical Engineering, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. FAU - Cai, Duan-Hua AU - Cai DH AD - College of Chemical Engineering, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. FAU - Hong, Ya-Zhen AU - Hong YZ AD - College of Chemical Engineering, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. AD - Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. AD - Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. FAU - Wang, Shi-Bin AU - Wang SB AD - College of Chemical Engineering, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. AD - Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. AD - Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. AD - Institute of Biomaterials and Tissue Engineering, Huaqiao University, Xiamen 361021, China. FAU - Liu, Yuan-Gang AU - Liu YG AD - College of Chemical Engineering, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. AD - Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. AD - Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, China, ygliu@hqu.edu.cn. LA - eng PT - Journal Article DEP - 20181204 PL - New Zealand TA - Int J Nanomedicine JT - International journal of nanomedicine JID - 101263847 RN - 0 (Drug Carriers) RN - 0 (RNA, Small Interfering) RN - 80168379AG (Doxorubicin) RN - 9002-98-6 (Polyethyleneimine) SB - IM MH - Apoptosis/drug effects MH - Cell Survival/drug effects MH - Doxorubicin/chemistry/pharmacology MH - Drug Carriers/*chemistry MH - HeLa Cells MH - Humans MH - Hydrogen-Ion Concentration MH - Magnetosomes/*chemistry MH - Magnetospirillum/*chemistry MH - Nanoparticles/*chemistry MH - Neoplasms/*drug therapy MH - Particle Size MH - Polyethyleneimine/chemical synthesis/chemistry MH - Proton Magnetic Resonance Spectroscopy MH - RNA, Small Interfering/genetics PMC - PMC6289231 OTO - NOTNLM OT - bacterial magnetosomes OT - co-delivery OT - gene therapy OT - pH-responsive release COIS- Disclosure The authors report no conflicts of interest in this work. EDAT- 2018/12/26 06:00 MHDA- 2019/02/05 06:00 PMCR- 2018/12/04 CRDT- 2018/12/26 06:00 PHST- 2018/12/26 06:00 [entrez] PHST- 2018/12/26 06:00 [pubmed] PHST- 2019/02/05 06:00 [medline] PHST- 2018/12/04 00:00 [pmc-release] AID - ijn-13-8269 [pii] AID - 10.2147/IJN.S180503 [doi] PST - epublish SO - Int J Nanomedicine. 2018 Dec 4;13:8269-8279. doi: 10.2147/IJN.S180503. eCollection 2018.