The effect of liposomal size on the targeted delivery of doxorubicin to Integrin αvβ3-expressing tumor endothelial cells

Kibria, Golam; Hatakeyama, Hiroto; Ohga, Noritaka; Hida, Kyoko; Harashima, Hideyoshi

doi:10.1016/j.biomaterials.2013.03.094

Cited by 103 publications

(70 citation statements)

References 47 publications

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“…Effect of the Growth Rate of the Cells on the Sensitivity to DOX To evaluate the effect of the cellular growth rate on the cytotoxic effect of DOX, we calculated the growth rate of the cancer cells following the protocol as we reported before (20). Based on the results presented in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…To inhibit the expression and function of P-gp, the cells were treated with Verapamil. [16][17][18] In the case of OSRC-2 cells, a class of RCC, which are intrinsically resistant to chemotherapy, [20][21][22][23][24] the EC 50 to DOX was calculated to be 71.15 µg/mL. Even though, the inhibition of P-gp by verapamil induces a 2-fold increment in the amount of internalized DOX (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…20) In a typical experiment, 5000 cells were seeded in 96-well plates and incubated overnight. The next day, the cells were exposed to different concentrations of DOX at 37°C for 8 h, followed by re-incubation for 16 h in the presence of fresh media.…”

Section: Methodsmentioning

confidence: 99%

“…Anderson Cancer Center, Houston, TX, U.S.A.) cells were cultured in Minimum Essential Medium (MEM) (GIBCO, Grand Island, NY, U.S.A.). 19) All of the medium mentioned above were supplemented with 10% fetal bovine serum (FBS) and penicillin (100 units/mL), streptomycin (100 µg/mL). The cells were cultured under an atmosphere of 5% CO 2 at 37°C.…”

Section: Methodsmentioning

confidence: 99%

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Comparative Study of the Sensitivities of Cancer Cells to Doxorubicin, and Relationships between the Effect of the Drug-Efflux Pump P-gp

Kibria

Hatakeyama

Akiyama

et al. 2014

Biological & Pharmaceutical Bulletin

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Multi-drug resistance (MDR) of cancers to chemotherapy including doxorubicin (DOX) is mediated by several factors. To design an effective therapy for the treatment of chemotherapy-resistant cancers, it is essential to explore the elements responsible for mediating MDR. However, exploring these factors in detail in a wide range of tumor types is challenging as several critical analytical steps are involved. Here, we demonstrated the way of exploring the factors mediating MDR in the tumor types without performing the analysis at the molecular level of cells. The sensitivities of 15 different types of cancer cells to DOX were evaluated, and the role of P-glycoprotein (P-gp), one of the major efflux-pumps, was explored. A correlation curve was developed between the intracellular amounts of DOX and the sensitivities of cells, and, based on this correlation, the cells were classified in response to the involvement of P-gp that mediates MDR. P-gp plays an active role in mediating MDR of cancer cells where a correlation between the sensitivities of cells and the accumulated DOX exists. In contrast, in cells that show a resistance to DOX but whose sensitivities are independent of the amount of accumulated drug, it was reasonably presumed that mechanisms other than P-gp are likely to be involved in mediating MDR. Based on the correlation between the availability of a drug and cell sensitivity, it would be reasonable to explore the factors governing cancer MDR, which is essential in designing an effective therapeutic approach for treating chemotherapy-resistant cancers using chemotherapeutic drugs.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Comparative Study of the Sensitivities of Cancer Cells to Doxorubicin, and Relationships between the Effect of the Drug-Efflux Pump P-gp

Kibria

Hatakeyama

Akiyama

et al. 2014

Biological & Pharmaceutical Bulletin

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“…Taken together, RGD-MEND appears to be tumor-specific, and therefore a safe carrier to TECs. We recently reported that a large RGD modified carrier (>300 nm) can efficiently target the tumor vasculature due to multivalent association between the carrier and its receptor [47]. Based on these new findings, an siRNA-encapsulating RGD-MEND would be an alternative strategy for anti-angiogenic therapy instead of a small molecule inhibitor and an antibody.…”

Section: Sirna Delivery To Tumors and The Tumor Vasculature Using A Pmentioning

confidence: 98%

“Programmed packaging” for gene delivery

Hyodo

Sakurai

Akita

et al. 2014

Journal of Controlled Release

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We report on the development of a Multifunctional Envelope-type Nano Device (MEND) based on our packaging concept "Programmed Packaging" to control not only intracellular trafficking but also the biodistribution of encapsulated compounds such as nucleic acids/proteins/peptides. Our strategy for achieving this is based on molecular mechanisms of cell biology such as endocytosis, vesicular trafficking, etc. In this review, we summarize the concept of programmed packaging and discuss some of our recent successful examples of using MENDs. Systematic evolution of ligands by exponential enrichment (SELEX) was applied as a new methodology for identifying a new ligand toward cell or mitochondria. The delivery of siRNA to tumors and the tumor vasculature was achieved using pH sensitive lipid (YSK05), which was newly designed and optimized under in vivo conditions. The efficient delivery of pDNA to immune cells such as dendritic cells has also been developed using the KALA ligand, which can be a breakthrough technology for DNA vaccine. Finally, ss-cleavable and pH-activated lipid-like surfactant (ssPalm) which is a lipid like material with pH-activatable and SS-cleavable properties is also introduced as a proof of our concept.

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