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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

Fiber-optic guided laser excitation triggered photo-thermal responsive liposomes release in vitro.Notes: (A) Illustration of apparatus. (B) Appearance of AuNP-liposome observed by transmission electron microscopy. (C) Particle size distribution of AuNP-liposome detected by dynamic laser scattering. (D) Contribution of AuNPs in photo-thermal responsive release of liposome. Data of (D) represent mean ± standard deviation (n=3).Abbreviations: AuNP, gold nanoparticle; DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine; DSPC, 1,2-distearoyl-sn-glycero-3-phosphatidylcholine; DSPE-PEG2k, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000].
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f4-ijn-10-5171: Fiber-optic guided laser excitation triggered photo-thermal responsive liposomes release in vitro.Notes: (A) Illustration of apparatus. (B) Appearance of AuNP-liposome observed by transmission electron microscopy. (C) Particle size distribution of AuNP-liposome detected by dynamic laser scattering. (D) Contribution of AuNPs in photo-thermal responsive release of liposome. Data of (D) represent mean ± standard deviation (n=3).Abbreviations: AuNP, gold nanoparticle; DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine; DSPC, 1,2-distearoyl-sn-glycero-3-phosphatidylcholine; DSPE-PEG2k, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000].

Mentions: In all, 2 mL 75 mM fluorescein entrapped liposome solution with a lipid concentration of 5 mg/mL was loaded in a 15×125 mm pyrex test tube with silicone seal, wrapped with aluminum foil and pre-warmed to 37°C by immersing in water bath. The solution was stimulated with 200 μm multi-mode optical fiber (FIBER-200-VIS, OceanOptics) guided 65 mW diode pumped solid-state laser (TWC Opto Corp, Taoyuan, Taiwan) with the emission end of the optical fiber was placed beneath the surface of the solution and 2 cm above the bottom of the test tube (Figure 4A). The fiber-coupled laser module had CW emission beam as circular spot with <5% power fluctuation, <0.5 nm spectral line-width and coupled into optical fiber with SubMiniature version A type connector. The self-quenching property of fluorescein at a concentration of 75 mM was used to quantify the percent fluorophore release from liposome. Fluorescein fluorescence is self-quenched inside the liposomes, but the fluorescence quenching is relieved after its release from liposome (Figure 2).34 Aliquots of 50 μL liposome solution were sampled at different intervals during laser excitation, then mixed with 50 μL isotonic saline, loaded in wells of 96-well plate, and their fluorescent emission intensities were measured by end-point detection of microplate reader (Synergy™ Mx Multi-Mode Microplate Reader, Biotek) applying 488 nm as an excitation wavelength and 520 nm as an emission wavelength. The percent fluorophore release was determined by the following formula: [(It − Ii)/(Id − Ii)] ×100%, where It was the measured intensity at time t, Id was the signal measured after liposome destruction by mixing aliquots of 50 μL liposome solution with 50 μL detergent (30 mM n-octyl-β-D-glucopyranoside), and Ii was the measured initial fluorescence. Consecutive triggered release of the AuNP-liposomes was tested in saline or rat plasma. Rat plasma was collected from tail vein of Sprague-Dawley rats (aged 17–19 weeks, 225±22.7 g) purchased from BioLASCO Taiwan Co, LTD (Yilan, Taiwan) after allowed to clot for a minimum of 45 minutes, and centrifugation at 2,000 rpm for 10 minutes to separate blood cells approved by the Institution Animal Care and Use Committee (IACUC) of National Chung Hsing University (IACUC Approval No 101–109).


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)

Fiber-optic guided laser excitation triggered photo-thermal responsive liposomes release in vitro.Notes: (A) Illustration of apparatus. (B) Appearance of AuNP-liposome observed by transmission electron microscopy. (C) Particle size distribution of AuNP-liposome detected by dynamic laser scattering. (D) Contribution of AuNPs in photo-thermal responsive release of liposome. Data of (D) represent mean ± standard deviation (n=3).Abbreviations: AuNP, gold nanoparticle; DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine; DSPC, 1,2-distearoyl-sn-glycero-3-phosphatidylcholine; DSPE-PEG2k, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000].
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4542555&req=5

f4-ijn-10-5171: Fiber-optic guided laser excitation triggered photo-thermal responsive liposomes release in vitro.Notes: (A) Illustration of apparatus. (B) Appearance of AuNP-liposome observed by transmission electron microscopy. (C) Particle size distribution of AuNP-liposome detected by dynamic laser scattering. (D) Contribution of AuNPs in photo-thermal responsive release of liposome. Data of (D) represent mean ± standard deviation (n=3).Abbreviations: AuNP, gold nanoparticle; DPPC, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine; DSPC, 1,2-distearoyl-sn-glycero-3-phosphatidylcholine; DSPE-PEG2k, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)-2000].
Mentions: In all, 2 mL 75 mM fluorescein entrapped liposome solution with a lipid concentration of 5 mg/mL was loaded in a 15×125 mm pyrex test tube with silicone seal, wrapped with aluminum foil and pre-warmed to 37°C by immersing in water bath. The solution was stimulated with 200 μm multi-mode optical fiber (FIBER-200-VIS, OceanOptics) guided 65 mW diode pumped solid-state laser (TWC Opto Corp, Taoyuan, Taiwan) with the emission end of the optical fiber was placed beneath the surface of the solution and 2 cm above the bottom of the test tube (Figure 4A). The fiber-coupled laser module had CW emission beam as circular spot with <5% power fluctuation, <0.5 nm spectral line-width and coupled into optical fiber with SubMiniature version A type connector. The self-quenching property of fluorescein at a concentration of 75 mM was used to quantify the percent fluorophore release from liposome. Fluorescein fluorescence is self-quenched inside the liposomes, but the fluorescence quenching is relieved after its release from liposome (Figure 2).34 Aliquots of 50 μL liposome solution were sampled at different intervals during laser excitation, then mixed with 50 μL isotonic saline, loaded in wells of 96-well plate, and their fluorescent emission intensities were measured by end-point detection of microplate reader (Synergy™ Mx Multi-Mode Microplate Reader, Biotek) applying 488 nm as an excitation wavelength and 520 nm as an emission wavelength. The percent fluorophore release was determined by the following formula: [(It − Ii)/(Id − Ii)] ×100%, where It was the measured intensity at time t, Id was the signal measured after liposome destruction by mixing aliquots of 50 μL liposome solution with 50 μL detergent (30 mM n-octyl-β-D-glucopyranoside), and Ii was the measured initial fluorescence. Consecutive triggered release of the AuNP-liposomes was tested in saline or rat plasma. Rat plasma was collected from tail vein of Sprague-Dawley rats (aged 17–19 weeks, 225±22.7 g) purchased from BioLASCO Taiwan Co, LTD (Yilan, Taiwan) after allowed to clot for a minimum of 45 minutes, and centrifugation at 2,000 rpm for 10 minutes to separate blood cells approved by the Institution Animal Care and Use Committee (IACUC) of National Chung Hsing University (IACUC Approval No 101–109).

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