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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

AuNP loading has no significant effect on T cell viability or function. T cells were loaded in the presence of 0.5 nM AuNPs for 24 h or cultured in medium alone and then measured for viability using Annexin-V/PI staining (A), proliferation using thymidine incorporation (B), migration through a transwell membrane in response to tumor (LCL) produced supernatant (C) and intracellular analysis of IFN-γ cytokine production following mitogen stimulation (D).
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Figure 2: AuNP loading has no significant effect on T cell viability or function. T cells were loaded in the presence of 0.5 nM AuNPs for 24 h or cultured in medium alone and then measured for viability using Annexin-V/PI staining (A), proliferation using thymidine incorporation (B), migration through a transwell membrane in response to tumor (LCL) produced supernatant (C) and intracellular analysis of IFN-γ cytokine production following mitogen stimulation (D).

Mentions: We next measured T cell viability and function post-AuNP loading to assess potential toxicity that may inhibit T cell performance as an in vivo delivery vehicle. Loading T cells with AuNPs had no immediate effect on T cell viability as determined by Annexin-V/7-AAD staining (Figure 2a) and did not alter the phenotype of the cells (Figure S2 in Additional file 1). Furthermore, there were no prolonged effects on T cell proliferation as measured by thymidine incorporation (Figure 2b). Importantly, AuNPs did not affect migration when tested in a transwell chemotaxis assay against supernatant produced from human LCL tumors, suggesting that T cells retain their migratory behavior post-AuNP loading (Figure 2c). Finally, production of IFN-γ following mitogen activation (PMA-I) was not impaired by AuNPs (Figure 2d). These results show that AuNPs have no detrimental effects on T cell viability and function in vitro and indicate that T cell migration in vivo will likely be retained following loading.


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)

AuNP loading has no significant effect on T cell viability or function. T cells were loaded in the presence of 0.5 nM AuNPs for 24 h or cultured in medium alone and then measured for viability using Annexin-V/PI staining (A), proliferation using thymidine incorporation (B), migration through a transwell membrane in response to tumor (LCL) produced supernatant (C) and intracellular analysis of IFN-γ cytokine production following mitogen stimulation (D).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: AuNP loading has no significant effect on T cell viability or function. T cells were loaded in the presence of 0.5 nM AuNPs for 24 h or cultured in medium alone and then measured for viability using Annexin-V/PI staining (A), proliferation using thymidine incorporation (B), migration through a transwell membrane in response to tumor (LCL) produced supernatant (C) and intracellular analysis of IFN-γ cytokine production following mitogen stimulation (D).
Mentions: We next measured T cell viability and function post-AuNP loading to assess potential toxicity that may inhibit T cell performance as an in vivo delivery vehicle. Loading T cells with AuNPs had no immediate effect on T cell viability as determined by Annexin-V/7-AAD staining (Figure 2a) and did not alter the phenotype of the cells (Figure S2 in Additional file 1). Furthermore, there were no prolonged effects on T cell proliferation as measured by thymidine incorporation (Figure 2b). Importantly, AuNPs did not affect migration when tested in a transwell chemotaxis assay against supernatant produced from human LCL tumors, suggesting that T cells retain their migratory behavior post-AuNP loading (Figure 2c). Finally, production of IFN-γ following mitogen activation (PMA-I) was not impaired by AuNPs (Figure 2d). These results show that AuNPs have no detrimental effects on T cell viability and function in vitro and indicate that T cell migration in vivo will likely be retained following loading.

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