Biodegradable amphiphilic poly(ethylene oxide)-block-polyesters with grafted polyamines as supramolecular nanocarriers for efficient siRNA delivery

Xiong, Xiao-Bing; Uludağ, Hasan; Lavasanifar, Afsaneh

doi:10.1016/j.biomaterials.2008.09.025

Cited by 163 publications

(138 citation statements)

References 59 publications

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“…The weak protection afforded by Lipofectamine 2000 was consistent with other reports that indicated the superior ability of polymers to protect siRNA against serum nucleases. 21,29 The lipid modification of PLL led to greater delivery of siRNA into the cells. PLL-StA enabled siRNA delivery to almost all cells ($90% by flow cytometry) but produced a significant drop in siRNA levels after 48 hours.…”

Section: Discussionmentioning

confidence: 99%

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Cationic polymer‐mediated small interfering RNA delivery for P‐glycoprotein down‐regulation in tumor cells

Abbasi¹,

Lavasanifar²,

Berthiaume³

et al. 2010

Cancer

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BACKGROUND: Among the treatment options that have been developed for cancer, chemotherapy remains 1 of the leading clinical approaches. Chemotherapy can usually control tumor growth at the onset of disease, but its effectiveness becomes limited by the overexpression of transporter proteins responsible for drug efflux, leading to multidrug resistance (MDR). To overcome this obstacle, the authors explored the feasibility of down-regulating the main drug transporter, Pglycoprotein (P-gp), by using nonviral small interfering RNA (siRNA) delivery as means to enhance the accumulation of chemotherapeutic agents in drug-resistant cancer cells. METHODS: Several cationic carriers capable of siRNA complexation were investigated for P-gp down-regulation in the MDA435/LCC6 cell line and, consequently, increased cellular uptake of the chemotherapeutic agents doxorubicin and paclitaxel. RESULTS: Efficient siRNA delivery into tumor cells was demonstrated particularly using a palmitic-acid substituted poly(L-lysine), with no apparent differences in siRNA delivery between the wild type (WT)-expressing and P-gp-expressing phenotype (MDR1) of the cells. Efficient siRNA delivery led to approximately 40% to 50% P-gp suppression (based on the average expression level of the protein), an approximately 3-fold increased DOX uptake, and increased cytotoxicity in MDR1 cells. CONCLUSIONS: The authors concluded that effective siRNA delivery with nonviral carriers can reduce the level of P-gp on cell surfaces and enhance the efficiency of chemotherapeutic agents in vitro. Cancer 2010;116:5544-54.

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Section: Discussionmentioning

confidence: 99%

“…6,29 The use of such a low siRNA concentration also is important for minimizing nonspecific (ie, off-target) siRNA activity. [32][33][34] With multiple siRNA treatments over 24-hour intervals, $40% to 50% P-gp suppression was gained after 72 hours using PLL-StA and Lipofectamine 2000.…”

Section: Original Article 5550mentioning

confidence: 99%

Cationic polymer‐mediated small interfering RNA delivery for P‐glycoprotein down‐regulation in tumor cells

Abbasi¹,

Lavasanifar²,

Berthiaume³

et al. 2010

Cancer

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“…23 Multifunctional nanocarriers with active targeting, cell membrane translocation and pH-triggered payload release were developed for co-delivery of nucleic acids with traditional cytotoxic drugs. 24,25 These nanocarriers showed improved cellular uptake of nucleic acids and cytotoxic drugs, leading to the enhanced cytotoxicity against drug-resistant cancer cells. Applications of multifunctional nanocarriers to drug-sensitive cancer treatment have also burst onto a scene with better therapeutic efficacy.…”

Section: Introductionmentioning

confidence: 99%

Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells

Hong

Shi

Qiao

et al. 2017

IJN

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Even though a tremendous number of multifunctional nanocarriers have been developed to tackle heterogeneous cancer cells, little attention has been paid to elucidate how to rationally design a multifunctional nanocarrier. In this study, three individual functions (active targeting, stimuli-triggered release and endo-lysosomal escape) were evaluated in doxorubicin (DOX)-sensitive MCF-7 cells and DOX-resistant MCF-7/ADR cells by constructing four kinds of micelles with active-targeting (AT-M), passive targeting, pH-triggered release ( pH T-M) and endo-lysosomal escape ( endo E-M) function, respectively. AT-M demonstrated the strongest cytotoxicity against MCF-7 cells and the highest cellular uptake of DOX due to the folate-mediated endocytosis. However, AT-M failed to exhibit the best efficacy against MCF-7/ADR cells, while endo E-M exhibited the strongest cytotoxicity against MCF-7/ADR cells and the highest cellular uptake of DOX due to the lowest elimination of DOX from the cells. This was attributed to the carrier-facilitated endo-lysosomal escape of DOX, which avoided exocytosis by lysosome secretion, resulting in an effective accumulation of DOX in the cytoplasm. The enhanced elimination of DOX from the MCF-7/ADR cells also accounted for the remarkable decrease in cytotoxicity against the cells of AT-M. Three micelles were further evaluated with MCF-7 cells and MCF-7/ADR-resistant cells xenografted mice model. In accordance with the in vitro results, AT-M and endo E-M demonstrated the strongest inhibition on the MCF-7 and MCF-7/ADR xenografted tumor, respectively. Active targeting and active targeting in combination with endo-lysosomal escape have been demonstrated to be the primary function for a nanocarrier against doxorubicin-sensitive and doxorubicin-resistant MCF-7 cells, respectively. These results indicate that the rational design of multifunctional nanocarriers for cancer therapy needs to consider the heterogeneous cancer cells and the primary function needs to be integrated to achieve effective payload delivery.

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“…[12][13][14] Hydrophobic modification of polycations has been explored as a potential solution. [15][16][17] For example, hydrophobized PEI derivatives have improved blood circulation time and higher transfection efficacy compared to parent PEI. [18][19][20][21] Hydrophobic modification of polycations with poly(lactide) (PLA) or poly(ε-caprolactone) (PCL) reduce the cytotoxicity of polycations while promoting the overall biodegradability of gene carriers.…”

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confidence: 99%

Dual Responsive, Stabilized Nanoparticles for Efficient In Vivo Plasmid Delivery

et al. 2013

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Biodegradable amphiphilic poly(ethylene oxide)-block-polyesters with grafted polyamines as supramolecular nanocarriers for efficient siRNA delivery

Cited by 163 publications

References 59 publications

Cationic polymer‐mediated small interfering RNA delivery for P‐glycoprotein down‐regulation in tumor cells

Cationic polymer‐mediated small interfering RNA delivery for P‐glycoprotein down‐regulation in tumor cells

Rational design of multifunctional micelles against doxorubicin-sensitive and doxorubicin-resistant MCF-7 human breast cancer cells

Dual Responsive, Stabilized Nanoparticles for Efficient In Vivo Plasmid Delivery

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