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Fiber-optic triggered release of liposome in vivo: implication of personalized chemotherapy.

Huang HL, Lu PH, Yang HC, Lee GD, Li HR, Liao KC - Int J Nanomedicine (2015)

Bottom Line: The pattern of topical release triggered by laser excitation conveyed through optical fibers was monitored by the increase in fluorescence resulting from the dilution of self-quenching (75 mM) fluorescein encapsulated in liposomes.In in vitro studies (in 37°C phosphate buffer saline), the AuNP-embedded liposomes showed a more efficient triggered release (74.53%±1.63% in 40 minutes) than traditional temperature-responsive liposomes without AuNPs (14.53%±3.17%) or AuNP-liposomes without excitation (21.92%±2.08%) by spectroscopic measurements.Furthermore, the preliminary results also suggested the tunable release capability of the system by demonstrating consecutive triggered releases with fiber-optic guided laser excitation.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung, Taiwan.

ABSTRACT
The aim of this research is to provide proof of principle by applying the fiber-optic triggered release of photo-thermally responsive liposomes embedded with gold nanoparticles (AuNPs) using a 200 μm fiber with 65 mW and 532 nm excitation for topical release in vivo. The tunable delivery function can be paired with an apoptosis biosensor based on the same fiber-optic configuration for providing real-time evaluation of chemotherapy efficacy in vivo to perform as a personalized chemotherapy system. The pattern of topical release triggered by laser excitation conveyed through optical fibers was monitored by the increase in fluorescence resulting from the dilution of self-quenching (75 mM) fluorescein encapsulated in liposomes. In in vitro studies (in 37°C phosphate buffer saline), the AuNP-embedded liposomes showed a more efficient triggered release (74.53%±1.63% in 40 minutes) than traditional temperature-responsive liposomes without AuNPs (14.53%±3.17%) or AuNP-liposomes without excitation (21.92%±2.08%) by spectroscopic measurements. Using the mouse xenograft studies, we first demonstrated that the encapsulation of fluorescein in liposomes resulted in a more substantial content retention (81%) in the tumor than for free fluorophores (14%) at 120 minutes after administration from in vivo fluorescence imaging. Furthermore, the preliminary results also suggested the tunable release capability of the system by demonstrating consecutive triggered releases with fiber-optic guided laser excitation.

No MeSH data available.


Related in: MedlinePlus

Effect of liposome encapsulation on diffusion of fluorophores in tumor.Notes: (A) Diffusion profile of 1 mM free fluorescein in tumor. (B) Diffusion profile of 1 mM fluorescein encapsulated liposome in tumor. (C) Quantification of diffusion profiles. The positions of tumors in (A) and (B) are indicated by the white arrowhead in the bright-field (BF) images. Data of (C) represent mean ± standard deviation (n=5).Abbreviation: AuNP, gold nanoparticle.
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f7-ijn-10-5171: Effect of liposome encapsulation on diffusion of fluorophores in tumor.Notes: (A) Diffusion profile of 1 mM free fluorescein in tumor. (B) Diffusion profile of 1 mM fluorescein encapsulated liposome in tumor. (C) Quantification of diffusion profiles. The positions of tumors in (A) and (B) are indicated by the white arrowhead in the bright-field (BF) images. Data of (C) represent mean ± standard deviation (n=5).Abbreviation: AuNP, gold nanoparticle.

Mentions: Malignant xenografts (MDA-MB 231 cell/matrigel™) were implanted subcutaneously into male nu/nu nude mice and allowed to grow into a solid mass with diameter from 1 cm to 2 cm. After anesthesia, the mice received a 50 μL bolus injection of either 1 mM fluorescein aqueous solution or 1 mM fluorescein encapsulated in AuNP-liposomes (the equivalent fluorescein concentration was 0.25 mM due to the dilution effect after purification with size-exclusive gel filtration to remove unencapsulated fluorescein; the lipid concentration was similarly diluted from 20 mg/mL after hydration to 5 mg/mL after purification). A 1 mM fluorescein aqueous solution was chosen because it had the highest concentration-dependent quantum yield, providing the strongest signal in studying the diffusion of fluorophores (within or without liposome) by fluorescent imaging. The time-dependent diffusion patterns of fluorophores (within or without liposome) were monitored by in vivo planar fluorescence imaging. The tumor boundary was delineated with specific fluorescence contour levels of pixels on bright-field (BF) images of mice at times after fluorophore (within or without liposome) injection, such as 0.5 at 0+ minute and 30 minutes, 0.25 at 60 minutes, and 0.071 at 120 minutes for the 1 mM fluorescein group (Figure 7A) or 0.5 at 0+ minute and 30 minutes, 0.3 at 60 minutes and 120 minutes for the liposome group (Figure 7B). The normalized fluorescence at the tumor area was calculated by dividing the sum of the fluorescence intensities of the pixels in the tumor (above the threshold contour level) at a specific time by the sum at 0+ minute (Figure 7C). It was found that liposome encapsulation yielded approximately 81% fluorophore retention (estimated by the normalized fluorescence intensity at the 120th minute) in the tumor 120 minutes after fluorophore injection (Figure 7C, red curve), while less than 14% free fluorophore retention was observed in the tumor 120 minutes after fluorophore injection (Figure 7C, green curve).


Fiber-optic triggered release of liposome in vivo: implication of personalized chemotherapy.

Huang HL, Lu PH, Yang HC, Lee GD, Li HR, Liao KC - Int J Nanomedicine (2015)

Effect of liposome encapsulation on diffusion of fluorophores in tumor.Notes: (A) Diffusion profile of 1 mM free fluorescein in tumor. (B) Diffusion profile of 1 mM fluorescein encapsulated liposome in tumor. (C) Quantification of diffusion profiles. The positions of tumors in (A) and (B) are indicated by the white arrowhead in the bright-field (BF) images. Data of (C) represent mean ± standard deviation (n=5).Abbreviation: AuNP, gold nanoparticle.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4542555&req=5

f7-ijn-10-5171: Effect of liposome encapsulation on diffusion of fluorophores in tumor.Notes: (A) Diffusion profile of 1 mM free fluorescein in tumor. (B) Diffusion profile of 1 mM fluorescein encapsulated liposome in tumor. (C) Quantification of diffusion profiles. The positions of tumors in (A) and (B) are indicated by the white arrowhead in the bright-field (BF) images. Data of (C) represent mean ± standard deviation (n=5).Abbreviation: AuNP, gold nanoparticle.
Mentions: Malignant xenografts (MDA-MB 231 cell/matrigel™) were implanted subcutaneously into male nu/nu nude mice and allowed to grow into a solid mass with diameter from 1 cm to 2 cm. After anesthesia, the mice received a 50 μL bolus injection of either 1 mM fluorescein aqueous solution or 1 mM fluorescein encapsulated in AuNP-liposomes (the equivalent fluorescein concentration was 0.25 mM due to the dilution effect after purification with size-exclusive gel filtration to remove unencapsulated fluorescein; the lipid concentration was similarly diluted from 20 mg/mL after hydration to 5 mg/mL after purification). A 1 mM fluorescein aqueous solution was chosen because it had the highest concentration-dependent quantum yield, providing the strongest signal in studying the diffusion of fluorophores (within or without liposome) by fluorescent imaging. The time-dependent diffusion patterns of fluorophores (within or without liposome) were monitored by in vivo planar fluorescence imaging. The tumor boundary was delineated with specific fluorescence contour levels of pixels on bright-field (BF) images of mice at times after fluorophore (within or without liposome) injection, such as 0.5 at 0+ minute and 30 minutes, 0.25 at 60 minutes, and 0.071 at 120 minutes for the 1 mM fluorescein group (Figure 7A) or 0.5 at 0+ minute and 30 minutes, 0.3 at 60 minutes and 120 minutes for the liposome group (Figure 7B). The normalized fluorescence at the tumor area was calculated by dividing the sum of the fluorescence intensities of the pixels in the tumor (above the threshold contour level) at a specific time by the sum at 0+ minute (Figure 7C). It was found that liposome encapsulation yielded approximately 81% fluorophore retention (estimated by the normalized fluorescence intensity at the 120th minute) in the tumor 120 minutes after fluorophore injection (Figure 7C, red curve), while less than 14% free fluorophore retention was observed in the tumor 120 minutes after fluorophore injection (Figure 7C, green curve).

Bottom Line: The pattern of topical release triggered by laser excitation conveyed through optical fibers was monitored by the increase in fluorescence resulting from the dilution of self-quenching (75 mM) fluorescein encapsulated in liposomes.In in vitro studies (in 37°C phosphate buffer saline), the AuNP-embedded liposomes showed a more efficient triggered release (74.53%±1.63% in 40 minutes) than traditional temperature-responsive liposomes without AuNPs (14.53%±3.17%) or AuNP-liposomes without excitation (21.92%±2.08%) by spectroscopic measurements.Furthermore, the preliminary results also suggested the tunable release capability of the system by demonstrating consecutive triggered releases with fiber-optic guided laser excitation.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Biomedical Engineering, National Chung Hsing University, Taichung, Taiwan.

ABSTRACT
The aim of this research is to provide proof of principle by applying the fiber-optic triggered release of photo-thermally responsive liposomes embedded with gold nanoparticles (AuNPs) using a 200 μm fiber with 65 mW and 532 nm excitation for topical release in vivo. The tunable delivery function can be paired with an apoptosis biosensor based on the same fiber-optic configuration for providing real-time evaluation of chemotherapy efficacy in vivo to perform as a personalized chemotherapy system. The pattern of topical release triggered by laser excitation conveyed through optical fibers was monitored by the increase in fluorescence resulting from the dilution of self-quenching (75 mM) fluorescein encapsulated in liposomes. In in vitro studies (in 37°C phosphate buffer saline), the AuNP-embedded liposomes showed a more efficient triggered release (74.53%±1.63% in 40 minutes) than traditional temperature-responsive liposomes without AuNPs (14.53%±3.17%) or AuNP-liposomes without excitation (21.92%±2.08%) by spectroscopic measurements. Using the mouse xenograft studies, we first demonstrated that the encapsulation of fluorescein in liposomes resulted in a more substantial content retention (81%) in the tumor than for free fluorophores (14%) at 120 minutes after administration from in vivo fluorescence imaging. Furthermore, the preliminary results also suggested the tunable release capability of the system by demonstrating consecutive triggered releases with fiber-optic guided laser excitation.

No MeSH data available.


Related in: MedlinePlus