Co-delivery of Doxorubicin and Bmi1 siRNA by Folate Receptor Targeted Liposomes Exhibits Enhanced Anti-Tumor Effects <i>in vitro</i> and <i>in vivo</i>

Tan, Yang; Li, Bin; Qi, Shibo; Liu, Yong; Gai, Yongkang; Ye, Peng; Yang, Guang; Zhang, Wendian; Zhang, Peng; He, Xingxing; Li, Weijie; Zhang, Zhiping; Xiang, Guangya; Xu, Cenke

doi:10.7150/thno.9423

Cited by 97 publications

(53 citation statements)

References 52 publications

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“…Combination therapy based on a siRNA and a chemical drug in a single NP platform has recently shown synergistic therapeutic efficacy in the treatment of many important diseases, such as cancer, skin inflammation, and rheumatoid arthritis 51-54. In this study, we developed an oral formulation (HA-functionalized NPs in hydrogel) for targeted co-delivery of a siRNA and a chemical drug to the key cells related to UC therapy (colonic epithelial cells and macrophages).…”

Section: Discussionmentioning

confidence: 99%

Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation

Xiao¹,

et al. 2016

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Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/CUR-NPs are featured by a desirable particle size (∼246 nm) and slightly negative zeta potential (∼-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98- or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation both in vitro and in vivo. This study shows the promising capability of the co-delivered siCD98 and CUR for boosting the conventional monotherapy via this novel nanotherapeutic agent, which offers a structurally simple platform for orally administered delivery of drugs to target cells in UC therapy.

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Section: Discussionmentioning

confidence: 99%

Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation

Xiao¹,

et al. 2016

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“…siRNA LPD Anti-EGFR Fab' The co-delivery LPD achieved the best control of tumor volume on orthotopic HCC-bearing mice, compared with the single agent-loaded LPD [59] Dox and BMI1 siRNA PEGylated cationic liposome Folic acid (FA) Bmi1 is an effective therapy target for siRNA-based cancer treatment, and it can be further improved by co-delivery of Dox via targeted liposomes [60] Docetaxel and VEGF siRNA Cationic liposome…”

Section: Cancer Resistance To Therapiesmentioning

confidence: 99%

“…The co-delivery formulation achieved the best control of tumor volume on orthotopic HCC-bearing mice, compared with the treatment of single agent-loaded LPDs. Yang et al encapsulated Dox in the aqueous core and adsorbed BMI1 siRNA on the surface of a folic acid (FA)-conjugated cationic liposome for the combination therapy of cancer [60]. The liposome prepared by thin-film hydration and membrane extrusion method consists of cholesterol (Chol), cationic lipid DOTAP, mPEG-DSPE and FA-PEG-Chol.…”

Section: Lipid-based Nanocarriers Liposomesmentioning

confidence: 99%

Nanocarriers for Delivery of siRNA and Co-Delivery of siRNA and Other Therapeutic Agents

Zhao

Feng

2015

Nanomedicine (Lond.)

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A major problem in cancer treatment is the multidrug resistance. siRNA inhibitors have great advantages to solve the problem, if the bottleneck of their delivery could be well addressed by the various nanocarriers. Moreover, co-delivery of siRNA together with the various anticancer agents in one nanocarrier may maximize their additive or synergistic effect. This review provides a comprehensive summary on the state-of-the-art of the nanocarriers, which may include prodrugs, micelles, liposomes, dendrimers, nanohydrogels, solid lipid nanoparticles, nanoparticles of biodegradable polymers and nucleic acid nanocarriers for delivery of siRNA and co-delivery of siRNA together with anticancer agents with focus on synthesis of the nanocarrier materials, design and characterization, in vitro and in vivo evaluation, and prospect and challenges of nanocarriers.

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“…Empty liposomes (L), L-DOX-NPs, and L-miR-375/DOX-NPs were synthesized (Figure S1) as previously described 20 . The average particle sizes of L, L-DOX-NPs, and L-miR-375/DOX-NPs detected by dynamic light scattering (DLS) were 117.7 ± 0.5, 122.4 ± 0.3, and 162.5 ± 0.7 nm, respectively, which indicated that L-miR-375/DOX-NPs could accumulate in liver easily.…”

Section: Resultsmentioning

confidence: 99%

MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma

Fan

Liao

Lü

et al. 2017

Molecular Therapy - Nucleic Acids

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Doxorubicin (DOX) is one of the most frequently used anti-cancer drugs and the front line option for hepatocellular carcinoma (HCC) treatment. However, the clinical applications of DOX are restricted largely due to its toxicity and chemoresistance. Here, we report that miR-375 and DOX were co-delivered by liposomes (named L-miR-375/DOX-NPs) for combination therapy of HCC and drug resistance reversion of DOX. In vitro, L-miR-375/DOX-NPs could deliver DOX and miR-375 efficiently and simultaneously into HCC cells and ensure the successful release of mature miR-375 and DOX. Then, the released miR-375 suppressed the malignant hallmarks of HCC by significantly decreasing the expression of AEG-1, YAP1, and ATG7, while the released DOX evidently accelerated cell apoptosis and blocked cycle at a G2/M stage by activating the P53/Bax/Bcl-2, caspase-3, and P-JNK, P-P38 pathway. Furthermore, miR-375 dramatically inhibited drug resistance of DOX by reducing the expression of multidrug resistance gene 1 (MDR1). In vivo, L-miR-375/DOX-NPs exhibited enhanced anti-tumor efficiency in xenograft HCC mouse models with mild adverse effects compared with doxorubicin or miR-375 alone. In conclusion, our research demonstrated that L-miR-375/DOX-NPs had significant synergetic anti-tumor effects and added values in overcoming drug resistance, which may represent a promising approach for the therapy of HCC.

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Co-delivery of Doxorubicin and Bmi1 siRNA by Folate Receptor Targeted Liposomes Exhibits Enhanced Anti-Tumor Effects in vitro and in vivo

Cited by 97 publications

References 52 publications

Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation

Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation

Nanocarriers for Delivery of siRNA and Co-Delivery of siRNA and Other Therapeutic Agents

MiR-375 and Doxorubicin Co-delivered by Liposomes for Combination Therapy of Hepatocellular Carcinoma

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