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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

Optimal composition of photo-thermal liposome.Notes: (A) Effect of AuNP concentration. DPPC:MPPC:DSPE-PEG2k (90:10:4) liposome with 33 ng/mL AuNP had photo-thermal conversion efficiency and stability among AuNP concentrations from 16 ng/mL to 66 ng/mL. (B) Effect of phospholipid compositions. Both DSPC:DPPC (90:10) and DPPC:Chol (80:20) liposomes had insufficient photo-thermal conversion efficiency and stability.Abbreviations: AuNP, gold nanoparticle; Chol, cholesterol; 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]; MPPC, 1-myristoyl-2-palmitoyl-sn-glycero-3-phosphotydilcholine.
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f6-ijn-10-5171: Optimal composition of photo-thermal liposome.Notes: (A) Effect of AuNP concentration. DPPC:MPPC:DSPE-PEG2k (90:10:4) liposome with 33 ng/mL AuNP had photo-thermal conversion efficiency and stability among AuNP concentrations from 16 ng/mL to 66 ng/mL. (B) Effect of phospholipid compositions. Both DSPC:DPPC (90:10) and DPPC:Chol (80:20) liposomes had insufficient photo-thermal conversion efficiency and stability.Abbreviations: AuNP, gold nanoparticle; Chol, cholesterol; 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]; MPPC, 1-myristoyl-2-palmitoyl-sn-glycero-3-phosphotydilcholine.

Mentions: Three of the most common thermal responsive liposomes formula, 90:10:4 (DPPC:MPPC:DSPE-PEG2k) or 90:10 (DSPC:DPPC), or 80:20 (DPPC:Chol), were tethered with AuNPs up to 132 ng/mL for exploring the optimal photo-responsive liposome for the fiber-optic guided laser triggered release study.17,26,27,39–42 The 90:10:4 (DPPC:MPPC:DSPE-PEG2k) liposome with 33 ng/mL AuNPs achieved the strongest photo-thermal conversion efficiency while maintaining decent liposome integrity at physiological temperature without causing significant leakage (21.92%±2.08% in 40 minutes without excitation) as shown in Figure 6. The AuNP-incorporated liposomes were spherical in shape with AuNPs appearing as black dots floating on the surface, and had a uniform particle size distribution, primarily around 100 nm, as observed by TEM (Figure 4B). Further examination with DLS analysis suggested that the particle size ranged primarily from 78 nm to 122 nm with an average value of 91.28±12.1 nm (Figure 4C), and had size distribution polydiversity index smaller than 0.121. The embedment of AuNPs in the lipo-some membrane under laser excitation significantly enhanced the permeability of the liposome and triggered more efficient release (74.53%±1.63% in 40 minutes, red solid curve) than liposomes without AuNPs (14.53%±3.17% in 40 minutes, black solid curve) or AuNP-liposomes without excitation (21.92%±2.08% in 40 minutes, red dot curve) in vitro (37°C water bath) as shown in Figure 4D.


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)

Optimal composition of photo-thermal liposome.Notes: (A) Effect of AuNP concentration. DPPC:MPPC:DSPE-PEG2k (90:10:4) liposome with 33 ng/mL AuNP had photo-thermal conversion efficiency and stability among AuNP concentrations from 16 ng/mL to 66 ng/mL. (B) Effect of phospholipid compositions. Both DSPC:DPPC (90:10) and DPPC:Chol (80:20) liposomes had insufficient photo-thermal conversion efficiency and stability.Abbreviations: AuNP, gold nanoparticle; Chol, cholesterol; 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]; MPPC, 1-myristoyl-2-palmitoyl-sn-glycero-3-phosphotydilcholine.
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f6-ijn-10-5171: Optimal composition of photo-thermal liposome.Notes: (A) Effect of AuNP concentration. DPPC:MPPC:DSPE-PEG2k (90:10:4) liposome with 33 ng/mL AuNP had photo-thermal conversion efficiency and stability among AuNP concentrations from 16 ng/mL to 66 ng/mL. (B) Effect of phospholipid compositions. Both DSPC:DPPC (90:10) and DPPC:Chol (80:20) liposomes had insufficient photo-thermal conversion efficiency and stability.Abbreviations: AuNP, gold nanoparticle; Chol, cholesterol; 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]; MPPC, 1-myristoyl-2-palmitoyl-sn-glycero-3-phosphotydilcholine.
Mentions: Three of the most common thermal responsive liposomes formula, 90:10:4 (DPPC:MPPC:DSPE-PEG2k) or 90:10 (DSPC:DPPC), or 80:20 (DPPC:Chol), were tethered with AuNPs up to 132 ng/mL for exploring the optimal photo-responsive liposome for the fiber-optic guided laser triggered release study.17,26,27,39–42 The 90:10:4 (DPPC:MPPC:DSPE-PEG2k) liposome with 33 ng/mL AuNPs achieved the strongest photo-thermal conversion efficiency while maintaining decent liposome integrity at physiological temperature without causing significant leakage (21.92%±2.08% in 40 minutes without excitation) as shown in Figure 6. The AuNP-incorporated liposomes were spherical in shape with AuNPs appearing as black dots floating on the surface, and had a uniform particle size distribution, primarily around 100 nm, as observed by TEM (Figure 4B). Further examination with DLS analysis suggested that the particle size ranged primarily from 78 nm to 122 nm with an average value of 91.28±12.1 nm (Figure 4C), and had size distribution polydiversity index smaller than 0.121. The embedment of AuNPs in the lipo-some membrane under laser excitation significantly enhanced the permeability of the liposome and triggered more efficient release (74.53%±1.63% in 40 minutes, red solid curve) than liposomes without AuNPs (14.53%±3.17% in 40 minutes, black solid curve) or AuNP-liposomes without excitation (21.92%±2.08% in 40 minutes, red dot curve) in vitro (37°C water bath) as shown in Figure 4D.

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