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Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery.

Xiao H, Wang L - Int J Nanomedicine (2015)

Bottom Line: To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized.Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method.Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People's Republic of China.

ABSTRACT
To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized. The formation of nanomicelles was proved with respect to the blue shift of the emission fluorescence as well as the fluorescent intensity increase of coumarin 6-loaded particles. The X-shaped polymers exhibited a smaller critical micelle concentration value and possessed higher micellar stability in comparison with those of linear ones. The size of X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles (XNMs) was much smaller than that of nanomicelles prepared with linear polymers. The reduction sensitivity of polymers was confirmed by the increase of micellar sizes as well as the in vitro drug release profile of DTX-loaded XNMs (DTX/XNMs). Cytotoxicity assays in vitro revealed that the blank XNMs were nontoxic against A2780 cells up to a concentration of 50 µg/mL, displaying good biocompatibility. DTX/XNMs were more toxic against A2780 cells than other formulations in both dose- and time-dependent manners. Cellular uptake assay displayed a higher intracellular drug delivery efficiency of XNMs than that of nanomicelles prepared with linear polymers. Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method. Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

No MeSH data available.


Related in: MedlinePlus

(A) Immunofluorescence images for nuclear staining (Hoechst33342: blue) and β-tubulin (FITC: green) following the treatment with different DTX formulations for 24 hours. (B) Fluorescence imaging analysis of apoptosis in A2780 cells.Abbreviations: DTX, docetaxel; XNMs, X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles; LNMs, loaded linear (PLGA)2-SS-4-arm-PEG200 polymer nanomicelles; FITC, fluorescein isothiocyanate; PLGA, poly(lactic-co-glycolic acid); PEG, poly(ethylene glycol).
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f10-ijn-10-5309: (A) Immunofluorescence images for nuclear staining (Hoechst33342: blue) and β-tubulin (FITC: green) following the treatment with different DTX formulations for 24 hours. (B) Fluorescence imaging analysis of apoptosis in A2780 cells.Abbreviations: DTX, docetaxel; XNMs, X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles; LNMs, loaded linear (PLGA)2-SS-4-arm-PEG200 polymer nanomicelles; FITC, fluorescein isothiocyanate; PLGA, poly(lactic-co-glycolic acid); PEG, poly(ethylene glycol).

Mentions: As shown in Figure 10A, the green fluorescent staining of tubulin in cells treated with XNMs exhibited a largely cytoplasmic distribution, just as the control did, and the distribution of staining of tubulin in cells treated with DTX revealed a slight decrease. In contrast, the cells incubated with micellar formulations showed a smaller green fluorescent staining distribution and more condensed microtubules around nuclei.42 The cells treated with DTX/XNMs exhibited the most condensed green fluorescence as they achieved the best effect on tubulin polymerization. The morphology of nuclei in cells treated with DTX-loaded nanomicelles became larger and more irregular in comparison with that of untreated cells. Besides, in comparison with other groups, the cells treated with DTX formulations decreased obviously.


Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery.

Xiao H, Wang L - Int J Nanomedicine (2015)

(A) Immunofluorescence images for nuclear staining (Hoechst33342: blue) and β-tubulin (FITC: green) following the treatment with different DTX formulations for 24 hours. (B) Fluorescence imaging analysis of apoptosis in A2780 cells.Abbreviations: DTX, docetaxel; XNMs, X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles; LNMs, loaded linear (PLGA)2-SS-4-arm-PEG200 polymer nanomicelles; FITC, fluorescein isothiocyanate; PLGA, poly(lactic-co-glycolic acid); PEG, poly(ethylene glycol).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4554410&req=5

f10-ijn-10-5309: (A) Immunofluorescence images for nuclear staining (Hoechst33342: blue) and β-tubulin (FITC: green) following the treatment with different DTX formulations for 24 hours. (B) Fluorescence imaging analysis of apoptosis in A2780 cells.Abbreviations: DTX, docetaxel; XNMs, X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles; LNMs, loaded linear (PLGA)2-SS-4-arm-PEG200 polymer nanomicelles; FITC, fluorescein isothiocyanate; PLGA, poly(lactic-co-glycolic acid); PEG, poly(ethylene glycol).
Mentions: As shown in Figure 10A, the green fluorescent staining of tubulin in cells treated with XNMs exhibited a largely cytoplasmic distribution, just as the control did, and the distribution of staining of tubulin in cells treated with DTX revealed a slight decrease. In contrast, the cells incubated with micellar formulations showed a smaller green fluorescent staining distribution and more condensed microtubules around nuclei.42 The cells treated with DTX/XNMs exhibited the most condensed green fluorescence as they achieved the best effect on tubulin polymerization. The morphology of nuclei in cells treated with DTX-loaded nanomicelles became larger and more irregular in comparison with that of untreated cells. Besides, in comparison with other groups, the cells treated with DTX formulations decreased obviously.

Bottom Line: To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized.Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method.Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, People's Republic of China.

ABSTRACT
To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized. The formation of nanomicelles was proved with respect to the blue shift of the emission fluorescence as well as the fluorescent intensity increase of coumarin 6-loaded particles. The X-shaped polymers exhibited a smaller critical micelle concentration value and possessed higher micellar stability in comparison with those of linear ones. The size of X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles (XNMs) was much smaller than that of nanomicelles prepared with linear polymers. The reduction sensitivity of polymers was confirmed by the increase of micellar sizes as well as the in vitro drug release profile of DTX-loaded XNMs (DTX/XNMs). Cytotoxicity assays in vitro revealed that the blank XNMs were nontoxic against A2780 cells up to a concentration of 50 µg/mL, displaying good biocompatibility. DTX/XNMs were more toxic against A2780 cells than other formulations in both dose- and time-dependent manners. Cellular uptake assay displayed a higher intracellular drug delivery efficiency of XNMs than that of nanomicelles prepared with linear polymers. Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method. Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

No MeSH data available.


Related in: MedlinePlus