Multifunctional nanocarrier mediated co-delivery of doxorubicin and siRNA for synergistic enhancement of glioma apoptosis in rat

Cheng, Du; Cao, Nuo; Chen, Jifeng; Yu, Xingsu; Shuai, Xintao

doi:10.1016/j.biomaterials.2011.10.057

Cited by 169 publications

(105 citation statements)

References 26 publications

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“…[45][46][47][48][49] In addition to delivering single therapeutics, there are growing interests in multiagent codelivery that can simultaneously incorporate and deliver multiple types of therapeutic payloads for combined therapy. [50][51][52] More importantly, these codelivery nanocarriers may potentially allow for the creation of synergetic effects to eventually improve overall treatment outcomes. 53,54 Recently, Zhu et al 49 reported using PLGA nanoparticles to codeliver docetaxel together with vitamin E TPGS, demonstrating their outstanding and optimized anticancer ability; Deng et al 54 coencapsulated a potent endogenous tumor-suppressive molecule, miR-34a, with doxorubicin into hyaluronic acid-chitosan nanoparticles, which were simultaneously delivered into breast cancer cells for improved therapeutic effects.…”

mentioning

confidence: 99%

Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

Zhou¹,

Duan²,

Zeng³

et al. 2015

IJN

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Natural product curcumin (Cur) and H 2 S-releasing prodrug SH-aspirin (SH-ASA) are potential anticancer agents with diverse mechanisms, but their clinical application prospects are restricted by hydrophobicity and limited efficiency. In this work, we coencapsulated SH-ASA and Cur into methoxy poly(ethylene glycol)-poly (lactide-coglycolide) (mPEG-PLGA) nanoparticles through a modified oil-in-water single-emulsion solvent evaporation process. The prepared SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles had a mean particle size of 122.3±6.8 nm and were monodispersed (polydispersity index =0.179±0.016) in water, with high drug-loading capacity and stability. Intriguingly, by treating with SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles, obvious synergistic anticancer effects on ES-2 and SKOV3 human ovarian carcinoma cells were observed in vitro, and activation of the mitochondrial apoptosis pathway was indicated. Our results demonstrated that SH-ASA/Cur-coloaded mPEG-PLGA nanoparticles could have potential clinical advantages for the treatment of ovarian cancer.

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confidence: 99%

Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

Zhou¹,

Duan²,

Zeng³

et al. 2015

IJN

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“…18,19 So far, co-delivery of anticancer drugs and siRNA has shown great potential in improving the potency of anticancer drugs, both in vitro and in vivo. 20,21 More importantly, the synergistic anticancer effects of siRNA targeting drug-resistance genes and chemotherapeutic drugs may be achieved. Upon functionalization of the nanocarriers with molecular-targeting ligands, tumor cell-specific delivery of both therapeutic agents may be realized simultaneously.…”

Section: Introductionmentioning

confidence: 99%

Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin

Shuai¹

2012

IJN

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A folate conjugated ternary copolymer, FA-PEG-PEI-PCL, of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(ε-caprolactone) (PCL) was synthesized. The copolymer self-assembled into cationic micelles capable of co-delivering siRNA and the anticancer drug doxorubicin (DOX). This dual functional nanocarrier demonstrated low cytotoxicity and high performance in drug/siRNA delivery. Upon the codelivery of siRNA, targeting the Bcl-2 gene, and DOX, using the folate-targeted nanocarrier, DOX-induced apoptosis in the skov-3 cells overexpressing folate receptor was significantly enhanced through a mechanism of downregulating the antiapoptotic protein Bcl-2, while simultaneously upregulating the proapoptotic protein Bax. This work suggested that the combination of Bcl-2 siRNA and DOX therapies is feasible, based on our dual functional nanocarrier, which set up a good basis for a future in vivo test.

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“…Because of this, the delivery of siRNA to the CNS has been mostly based on invasive administrations of naked or electrostatically complexed siRNA with cationic lipids or polymers. For instance intraventricular injection, 15,16 perilesional stereotactic injections, 17 direct injection in the hippocampus 18 or in the right striatum, 19 convection-enhanced delivery, 20 and local electroporation 21 have been used to knock down different exogenous or endogenous genes. Other approaches less explored, that do not involve direct neuronal uptake, rely on the intravenous administration of siRNA or its complexes coupled to ligands targeted to receptors on the brain capillary endothelial cell, such as the transferrin receptor, 22 the nicotinic acetylcholine receptor, 23 the low-density lipoprotein receptor, 24,25 or the rabies virus glycoprotein peptide.…”

Section: Introductionmentioning

confidence: 99%

Increased brain radioactivity by intranasal 32P-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels

Perez¹,

Mundiña‐Weilenmann²,

Romero³

et al. 2012

IJN

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Background: Molecules taken up by olfactory and trigeminal nerve neurons directly access the brain by the nose-to-brain pathway. In situ-forming mucoadhesive gels would increase the residence time of intranasal material, favoring the nose-to-brain delivery. In this first approach, brain radioactivity after intranasal administration of 32 P-small interference RNA (siRNA) complexed with poly(amidoamine) G7 dendrimers (siRNA dendriplexes) within in situ-forming mucoadhesive gels, was determined. Materials:32 P-siRNA dendriplexes were incorporated into in situ-forming mucoadhesive gels prepared by blending thermosensitive poloxamer (23% w/w) with mucoadhesive chitosan (1% w/w, PxChi) or carbopol (0.25% w/w, PxBCP). Rheological properties, radiolabel release profile, and local toxicity in rat nasal mucosa were determined. The best-suited formulation was intranasally administered to rats, and blood absorption and brain distribution of radioactivity were measured. Results:The gelation temperature of both formulations was 23°C. The PxChi liquid showed non-Newtonian pseudoplastic behavior of high consistency and difficult manipulation, and the gel retained 100% of radiolabel after 150 minutes. The PxCBP liquid showed a Newtonian behavior of low viscosity and easy manipulation, while in the gel phase showed apparent viscosity similar to that of the mucus but higher than that of aqueous solution. The gel released 35% of radiolabel and the released material showed silencing activity in vitro. Three intranasal doses of dendriplexes in PxCBP gel did not damage the rat nasal mucosa. A combination of 32 P-siRNA complexation with dendrimers, incorporation of the dendriplexes into PxCBP gel, and administration of two intranasal doses was necessary to achieve higher brain radioactivity than that achieved by intravenous dendriplexes or intranasal naked siRNA. Conclusion:The increased radioactivity within the olfactory bulb suggested that the combination above mentioned favored the mediation of a direct brain delivery.

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Multifunctional nanocarrier mediated co-delivery of doxorubicin and siRNA for synergistic enhancement of glioma apoptosis in rat

Cited by 169 publications

References 26 publications

Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

Codelivery of SH-aspirin and curcumin by mPEG-PLGA nanoparticles enhanced antitumor activity by inducing mitochondrial apoptosis

Enhanced apoptosis of ovarian cancer cells via nanocarrier-mediated codelivery of siRNA and doxorubicin

Increased brain radioactivity by intranasal 32P-labeled siRNA dendriplexes within in situ-forming mucoadhesive gels

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