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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-T cells enhance the delivery of gold nanoparticles to the tumor site in vivo. Tumor-bearing mice were injected i.v. with PEG-AuNPs or AuNP-T cells. Tumors were subsequently resected at various time points and measured for AuNP content using ICP-MS. Values displayed represent the percentage of injected gold normalized for tumor dry weight differences (mean ± SEM). The percentage of gold delivered by the AuNP-T cells at 48 h represents a significant, four-fold increase over the PEG-AuNP group at 24 h (P < 0.01).
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Figure 5: AuNP-T cells enhance the delivery of gold nanoparticles to the tumor site in vivo. Tumor-bearing mice were injected i.v. with PEG-AuNPs or AuNP-T cells. Tumors were subsequently resected at various time points and measured for AuNP content using ICP-MS. Values displayed represent the percentage of injected gold normalized for tumor dry weight differences (mean ± SEM). The percentage of gold delivered by the AuNP-T cells at 48 h represents a significant, four-fold increase over the PEG-AuNP group at 24 h (P < 0.01).

Mentions: Closer examination of LCL tumors following treatment with either PEG-AuNPs or AuNP-T cells showed an increase in AuNP delivery to tumors following cellular transport. For PEG-AuNPs, the highest level of accumulation in tumors was observed at 24 h post-injection, while peak tumor gold accumulation following T cell delivery was seen at 48 h. Using PEG-AuNP, ICP-MS analysis of gold content of excised tumor tissue showed that 0.39 ± 0.33% of ID reached the tumor at 24 h. Whereas, using AuNP-T cells, 1.55 ± 0.72% of the ID localized to the tumor at 48 h (P < 0.01) (Figure 5). This represents a four-fold increase in the efficiency of AuNP delivery to the tumor site using T cells as vehicles.


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-T cells enhance the delivery of gold nanoparticles to the tumor site in vivo. Tumor-bearing mice were injected i.v. with PEG-AuNPs or AuNP-T cells. Tumors were subsequently resected at various time points and measured for AuNP content using ICP-MS. Values displayed represent the percentage of injected gold normalized for tumor dry weight differences (mean ± SEM). The percentage of gold delivered by the AuNP-T cells at 48 h represents a significant, four-fold increase over the PEG-AuNP group at 24 h (P < 0.01).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: AuNP-T cells enhance the delivery of gold nanoparticles to the tumor site in vivo. Tumor-bearing mice were injected i.v. with PEG-AuNPs or AuNP-T cells. Tumors were subsequently resected at various time points and measured for AuNP content using ICP-MS. Values displayed represent the percentage of injected gold normalized for tumor dry weight differences (mean ± SEM). The percentage of gold delivered by the AuNP-T cells at 48 h represents a significant, four-fold increase over the PEG-AuNP group at 24 h (P < 0.01).
Mentions: Closer examination of LCL tumors following treatment with either PEG-AuNPs or AuNP-T cells showed an increase in AuNP delivery to tumors following cellular transport. For PEG-AuNPs, the highest level of accumulation in tumors was observed at 24 h post-injection, while peak tumor gold accumulation following T cell delivery was seen at 48 h. Using PEG-AuNP, ICP-MS analysis of gold content of excised tumor tissue showed that 0.39 ± 0.33% of ID reached the tumor at 24 h. Whereas, using AuNP-T cells, 1.55 ± 0.72% of the ID localized to the tumor at 48 h (P < 0.01) (Figure 5). This represents a four-fold increase in the efficiency of AuNP delivery to the tumor site using T cells as vehicles.

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