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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

Gold nanoparticle uptake by human T cells. (A) TEM imaging of gold colloid (diameter = 40-45 nm). (B) Brightfield (upper) and darkfield (lower) images of human T cells demonstrate gold nanoparticle uptake by the increased light scattering seen in the AuNP-T cell group compared to T cells alone. (C) ICP-OES analysis of T cell gold content at 24 h using different nanoparticle loading concentrations. Each point is a composite of data acquired from three different T cell donors. (D) Time course data for T cells from a single donor loaded with different concentrations of gold nanoparticles. Optimal loading occurred after 24 h at a concentration between 0.5 and 1.0 nM.
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Figure 1: Gold nanoparticle uptake by human T cells. (A) TEM imaging of gold colloid (diameter = 40-45 nm). (B) Brightfield (upper) and darkfield (lower) images of human T cells demonstrate gold nanoparticle uptake by the increased light scattering seen in the AuNP-T cell group compared to T cells alone. (C) ICP-OES analysis of T cell gold content at 24 h using different nanoparticle loading concentrations. Each point is a composite of data acquired from three different T cell donors. (D) Time course data for T cells from a single donor loaded with different concentrations of gold nanoparticles. Optimal loading occurred after 24 h at a concentration between 0.5 and 1.0 nM.

Mentions: Synthesized gold colloid was determined to be 40-45 nm in diameter by transmission electron microscopy (TEM) (Figure 1a and Figure S1 in Additional file 1). Activated and expanded human T cells were cultured in the presence of AuNPs for a period of 1 to 24 h to permit AuNP internalization. AuNP loading was confirmed using bright field and dark field microscopy demonstrating that T cells co-localize with AuNPs (Figure 1b). We further optimized loading conditions by altering AuNP concentration (per cell) and time of incubation. To determine the number of nanoparticles present per T cell, an inductively coupled plasma optical emission spectrometry (ICP-OES) analysis was used. T cells from three different human donors were first cultured with concentrations of AuNPs ranging from 0.05 to 0.5 nM for a period of 24 h to evaluate for variability in gold nanoparticle loading due to differences in T cells from different donors (Figure 1c). A maximum of 14,900 ± 2,400 AuNPs was internalized per T cell using a AuNP loading concentration of 0.5 nM (Figure 1c). We then performed a time course study using T cells from a single donor to determine the minimum amount of time required to load the T cells with the maximum number of AuNPs (Figure 1d). For this study, we incubated T cells with nanoparticle concentrations ranging from 0.05 to 1 nM. At 24 h, the 0.5 and 1 nM groups have similar gold content, suggesting that there is a maximum amount of AuNPs that can be internalized by T cells. These results demonstrate that maximal AuNP loading of T cells can be achieved using a concentration of 0.5 nM AuNP and an incubation period of 24 h.


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)

Gold nanoparticle uptake by human T cells. (A) TEM imaging of gold colloid (diameter = 40-45 nm). (B) Brightfield (upper) and darkfield (lower) images of human T cells demonstrate gold nanoparticle uptake by the increased light scattering seen in the AuNP-T cell group compared to T cells alone. (C) ICP-OES analysis of T cell gold content at 24 h using different nanoparticle loading concentrations. Each point is a composite of data acquired from three different T cell donors. (D) Time course data for T cells from a single donor loaded with different concentrations of gold nanoparticles. Optimal loading occurred after 24 h at a concentration between 0.5 and 1.0 nM.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Gold nanoparticle uptake by human T cells. (A) TEM imaging of gold colloid (diameter = 40-45 nm). (B) Brightfield (upper) and darkfield (lower) images of human T cells demonstrate gold nanoparticle uptake by the increased light scattering seen in the AuNP-T cell group compared to T cells alone. (C) ICP-OES analysis of T cell gold content at 24 h using different nanoparticle loading concentrations. Each point is a composite of data acquired from three different T cell donors. (D) Time course data for T cells from a single donor loaded with different concentrations of gold nanoparticles. Optimal loading occurred after 24 h at a concentration between 0.5 and 1.0 nM.
Mentions: Synthesized gold colloid was determined to be 40-45 nm in diameter by transmission electron microscopy (TEM) (Figure 1a and Figure S1 in Additional file 1). Activated and expanded human T cells were cultured in the presence of AuNPs for a period of 1 to 24 h to permit AuNP internalization. AuNP loading was confirmed using bright field and dark field microscopy demonstrating that T cells co-localize with AuNPs (Figure 1b). We further optimized loading conditions by altering AuNP concentration (per cell) and time of incubation. To determine the number of nanoparticles present per T cell, an inductively coupled plasma optical emission spectrometry (ICP-OES) analysis was used. T cells from three different human donors were first cultured with concentrations of AuNPs ranging from 0.05 to 0.5 nM for a period of 24 h to evaluate for variability in gold nanoparticle loading due to differences in T cells from different donors (Figure 1c). A maximum of 14,900 ± 2,400 AuNPs was internalized per T cell using a AuNP loading concentration of 0.5 nM (Figure 1c). We then performed a time course study using T cells from a single donor to determine the minimum amount of time required to load the T cells with the maximum number of AuNPs (Figure 1d). For this study, we incubated T cells with nanoparticle concentrations ranging from 0.05 to 1 nM. At 24 h, the 0.5 and 1 nM groups have similar gold content, suggesting that there is a maximum amount of AuNPs that can be internalized by T cells. These results demonstrate that maximal AuNP loading of T cells can be achieved using a concentration of 0.5 nM AuNP and an incubation period of 24 h.

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