Abstract
In cancer research there is a fundamental need for animal models that allow the in vivo longitudinal visualization and quantification of tumor development, nanotherapeutic delivery, the tumor microenvironment including blood vessels, macrophages, fibroblasts, immune cells, and extracellular matrix, and the tissue response to treatment. To address this need, we developed a novel mouse ocular xenograft model. Green fluorescent protein (GFP) expressing human glioblastoma cells (between 500 and 10,000) were implanted into the subretinal space of immunodeficient mice (56 eyes). The resultant xenografts were imaged in vivo non-invasively with combined fluorescence scanning laser ophthalmoscopy (SLO) and volumetric optical coherence tomography (OCT) for a period up to several months. Most xenografts exhibited a latent phase followed by a stable or rapidly increasing volume, but about 1/3 underwent spontaneous remission. After prescribed growth, a population of tumors was treated with intravenously delivered doxorubicin-containing porphyrin and cholic acid-based nanoparticles (“nanodox”). Fluorescence resonance energy transfer (FRET) emission (doxorubicin → porphyrin) was used to localize nanodox in the xenografts, and 690 nm light exposure to activate it. Such photo-nanotherapy was highly effective in reducing tumor volume. Histopathology and flow cytometry revealed CD4 + and CD8 + immune cell infiltration of xenografts. Overall, the ocular model shows potential for examining the relationships between neoplastic growth, neovascularization and other features of the immune microenvironment, and for evaluating treatment response longitudinally in vivo.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 151-166 |
| Number of pages | 16 |
| Journal | Biomedical Optics Express |
| Volume | 10 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2019 |
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ASJC Scopus subject areas
- Biotechnology
- Atomic and Molecular Physics, and Optics
Cite this
Novel window for cancer nanotheranostics : Non-invasive ocular assessments of tumor growth and nanotherapeutic treatment efficacy in vivo. / Goswami, Mayank; Wang, Xinlei; Zhang, Pengfei; Xiao, Wenwu; Karlen, Sarah J.; Li, Yuanpei; Zawadzki, Robert; Burns, Marie E; Lam, Kit; Pugh Jr, Edward N.
In: Biomedical Optics Express, Vol. 10, No. 1, 01.01.2019, p. 151-166.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel window for cancer nanotheranostics
T2 - Non-invasive ocular assessments of tumor growth and nanotherapeutic treatment efficacy in vivo
AU - Goswami, Mayank
AU - Wang, Xinlei
AU - Zhang, Pengfei
AU - Xiao, Wenwu
AU - Karlen, Sarah J.
AU - Li, Yuanpei
AU - Zawadzki, Robert
AU - Burns, Marie E
AU - Lam, Kit
AU - Pugh Jr, Edward N
PY - 2019/1/1
Y1 - 2019/1/1
N2 - In cancer research there is a fundamental need for animal models that allow the in vivo longitudinal visualization and quantification of tumor development, nanotherapeutic delivery, the tumor microenvironment including blood vessels, macrophages, fibroblasts, immune cells, and extracellular matrix, and the tissue response to treatment. To address this need, we developed a novel mouse ocular xenograft model. Green fluorescent protein (GFP) expressing human glioblastoma cells (between 500 and 10,000) were implanted into the subretinal space of immunodeficient mice (56 eyes). The resultant xenografts were imaged in vivo non-invasively with combined fluorescence scanning laser ophthalmoscopy (SLO) and volumetric optical coherence tomography (OCT) for a period up to several months. Most xenografts exhibited a latent phase followed by a stable or rapidly increasing volume, but about 1/3 underwent spontaneous remission. After prescribed growth, a population of tumors was treated with intravenously delivered doxorubicin-containing porphyrin and cholic acid-based nanoparticles (“nanodox”). Fluorescence resonance energy transfer (FRET) emission (doxorubicin → porphyrin) was used to localize nanodox in the xenografts, and 690 nm light exposure to activate it. Such photo-nanotherapy was highly effective in reducing tumor volume. Histopathology and flow cytometry revealed CD4 + and CD8 + immune cell infiltration of xenografts. Overall, the ocular model shows potential for examining the relationships between neoplastic growth, neovascularization and other features of the immune microenvironment, and for evaluating treatment response longitudinally in vivo.
AB - In cancer research there is a fundamental need for animal models that allow the in vivo longitudinal visualization and quantification of tumor development, nanotherapeutic delivery, the tumor microenvironment including blood vessels, macrophages, fibroblasts, immune cells, and extracellular matrix, and the tissue response to treatment. To address this need, we developed a novel mouse ocular xenograft model. Green fluorescent protein (GFP) expressing human glioblastoma cells (between 500 and 10,000) were implanted into the subretinal space of immunodeficient mice (56 eyes). The resultant xenografts were imaged in vivo non-invasively with combined fluorescence scanning laser ophthalmoscopy (SLO) and volumetric optical coherence tomography (OCT) for a period up to several months. Most xenografts exhibited a latent phase followed by a stable or rapidly increasing volume, but about 1/3 underwent spontaneous remission. After prescribed growth, a population of tumors was treated with intravenously delivered doxorubicin-containing porphyrin and cholic acid-based nanoparticles (“nanodox”). Fluorescence resonance energy transfer (FRET) emission (doxorubicin → porphyrin) was used to localize nanodox in the xenografts, and 690 nm light exposure to activate it. Such photo-nanotherapy was highly effective in reducing tumor volume. Histopathology and flow cytometry revealed CD4 + and CD8 + immune cell infiltration of xenografts. Overall, the ocular model shows potential for examining the relationships between neoplastic growth, neovascularization and other features of the immune microenvironment, and for evaluating treatment response longitudinally in vivo.
UR - http://www.scopus.com/inward/record.url?scp=85061530329&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85061530329&partnerID=8YFLogxK
U2 - 10.1364/BOE.10.000151
DO - 10.1364/BOE.10.000151
M3 - Article
AN - SCOPUS:85061530329
VL - 10
SP - 151
EP - 166
JO - Biomedical Optics Express
JF - Biomedical Optics Express
SN - 2156-7085
IS - 1
ER -