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T cells enhance gold nanoparticle delivery to tumors in vivo.

Kennedy LC, Bear AS, Young JK, Lewinski NA, Kim J, Foster AE, Drezek RA - Nanoscale Res Lett (2011)

Bottom Line: We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production).In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution.Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, USA. aefoster@txccc.org.

ABSTRACT
Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

No MeSH data available.


Related in: MedlinePlus

Biodistribution comparison of AuNPs and AuNP-T cells in mice. Mice were injected with PEG-AuNPs (60-65 nm hydrodynamic diameter), AuNP-T cells, or PBS and subsequently sacrificed at various time points to determine biodistribution. PBS gold levels were negligible in comparison to AuNP and AuNP-T cell groups for all organs. Values are percentage of the injected gold dose (%ID) were calculated from ICP-MS and are normalized for dry weight differences. The AuNP-T cell group exhibited significantly higher gold delivery to the lungs, liver, and bone, while the AuNP group demonstrated higher gold levels within the small intestine. No significant differences were seen in the spleen, kidney, muscle, or brain. An asterisk indicates statistically significant (P < 0.05) differences.
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Figure 4: Biodistribution comparison of AuNPs and AuNP-T cells in mice. Mice were injected with PEG-AuNPs (60-65 nm hydrodynamic diameter), AuNP-T cells, or PBS and subsequently sacrificed at various time points to determine biodistribution. PBS gold levels were negligible in comparison to AuNP and AuNP-T cell groups for all organs. Values are percentage of the injected gold dose (%ID) were calculated from ICP-MS and are normalized for dry weight differences. The AuNP-T cell group exhibited significantly higher gold delivery to the lungs, liver, and bone, while the AuNP group demonstrated higher gold levels within the small intestine. No significant differences were seen in the spleen, kidney, muscle, or brain. An asterisk indicates statistically significant (P < 0.05) differences.

Mentions: We next performed a comprehensive in vivo biodistribution study using inductively coupled plasma mass spectrometry (ICP-MS) and ICP-OES to map the location of free PEGylated AuNPs (40-45 nm gold colloid coated with 5000 MW PEG) and AuNPs delivered by T cells. Prior to injection, ICP-OES was performed to determine the absolute gold dose for PEG-AuNPs and AuNP-T cells. Following intravenous injection with PEG-AuNPs or AuNP-T cells, tumors, and organs (bone, brain, heart, intestine, kidney, liver, lungs, muscle, plasma, and spleen) were harvested and analyzed for gold levels using ICP-MS. For PEG-AuNP treated mice, organs were harvested at 4, 8, 24, and 48 h post-injection, while for AuNP-T cell treated mice, organs were harvested at 24 and 48 h (Figure 4a). Predictably, the biodistribution of AuNP-T cells is altered when compared to that of the PEG-AuNPs. As observed in previous studies [13,15], the highest percentages of AuNPs using PEG coating were delivered to the liver and spleen (5.65 and 17.03%, respectively, at 48 h, Figure 4b,c). In comparison, T cells delivered AuNPs to the lung, liver, and spleen, which received 4.76, 33.5, and 2.69% at 48 h, respectively (Figure 4b and 4c). The plasma half-life of the PEG-AuNPs was calculated to be 6.05 h, and no gold was detected in the plasma for the AuNP-T cell group, suggesting no significant AuNP leakage from the T cells during in vivo migration. The AuNP-T cell biodistribution over time correlates with the normal biodistribution of human T cells, suggesting that the presence of internalized AuNPs does not significantly change the T cell biodistribution [32]. These data suggest that cellular delivery of AuNP will result in a unique biodistribution pattern that is dependent on the cell type used for delivery.


T cells enhance gold nanoparticle delivery to tumors in vivo.

Kennedy LC, Bear AS, Young JK, Lewinski NA, Kim J, Foster AE, Drezek RA - Nanoscale Res Lett (2011)

Biodistribution comparison of AuNPs and AuNP-T cells in mice. Mice were injected with PEG-AuNPs (60-65 nm hydrodynamic diameter), AuNP-T cells, or PBS and subsequently sacrificed at various time points to determine biodistribution. PBS gold levels were negligible in comparison to AuNP and AuNP-T cell groups for all organs. Values are percentage of the injected gold dose (%ID) were calculated from ICP-MS and are normalized for dry weight differences. The AuNP-T cell group exhibited significantly higher gold delivery to the lungs, liver, and bone, while the AuNP group demonstrated higher gold levels within the small intestine. No significant differences were seen in the spleen, kidney, muscle, or brain. An asterisk indicates statistically significant (P < 0.05) differences.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3211348&req=5

Figure 4: Biodistribution comparison of AuNPs and AuNP-T cells in mice. Mice were injected with PEG-AuNPs (60-65 nm hydrodynamic diameter), AuNP-T cells, or PBS and subsequently sacrificed at various time points to determine biodistribution. PBS gold levels were negligible in comparison to AuNP and AuNP-T cell groups for all organs. Values are percentage of the injected gold dose (%ID) were calculated from ICP-MS and are normalized for dry weight differences. The AuNP-T cell group exhibited significantly higher gold delivery to the lungs, liver, and bone, while the AuNP group demonstrated higher gold levels within the small intestine. No significant differences were seen in the spleen, kidney, muscle, or brain. An asterisk indicates statistically significant (P < 0.05) differences.
Mentions: We next performed a comprehensive in vivo biodistribution study using inductively coupled plasma mass spectrometry (ICP-MS) and ICP-OES to map the location of free PEGylated AuNPs (40-45 nm gold colloid coated with 5000 MW PEG) and AuNPs delivered by T cells. Prior to injection, ICP-OES was performed to determine the absolute gold dose for PEG-AuNPs and AuNP-T cells. Following intravenous injection with PEG-AuNPs or AuNP-T cells, tumors, and organs (bone, brain, heart, intestine, kidney, liver, lungs, muscle, plasma, and spleen) were harvested and analyzed for gold levels using ICP-MS. For PEG-AuNP treated mice, organs were harvested at 4, 8, 24, and 48 h post-injection, while for AuNP-T cell treated mice, organs were harvested at 24 and 48 h (Figure 4a). Predictably, the biodistribution of AuNP-T cells is altered when compared to that of the PEG-AuNPs. As observed in previous studies [13,15], the highest percentages of AuNPs using PEG coating were delivered to the liver and spleen (5.65 and 17.03%, respectively, at 48 h, Figure 4b,c). In comparison, T cells delivered AuNPs to the lung, liver, and spleen, which received 4.76, 33.5, and 2.69% at 48 h, respectively (Figure 4b and 4c). The plasma half-life of the PEG-AuNPs was calculated to be 6.05 h, and no gold was detected in the plasma for the AuNP-T cell group, suggesting no significant AuNP leakage from the T cells during in vivo migration. The AuNP-T cell biodistribution over time correlates with the normal biodistribution of human T cells, suggesting that the presence of internalized AuNPs does not significantly change the T cell biodistribution [32]. These data suggest that cellular delivery of AuNP will result in a unique biodistribution pattern that is dependent on the cell type used for delivery.

Bottom Line: We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production).In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution.Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Bioengineering, Rice University, Houston, TX 77005, USA. aefoster@txccc.org.

ABSTRACT
Gold nanoparticle-mediated photothermal therapy (PTT) has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs) are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR) effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production). Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

No MeSH data available.


Related in: MedlinePlus