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Near-infrared fluorescent imaging of metastatic ovarian cancer using folate receptor-targeted high-density lipoprotein nanocarriers.

ABSTRACT: AIM:The targeting efficiency of folate receptor-? (FR-?)-targeted high-density lipoprotein nanoparticles (HDL NPs) was evaluated in a syngeneic mouse model of ovarian cancer. MATERIALS & METHODS:Folic acid was conjugated to the surface of fluorescent-labeled HDL NPs. In vivo tumor targeting of folic acid-HDL NPs and HDL NPs were evaluated in mice with metastatic ovarian cancer following intravenous or intraperitoneal (ip.) administration. RESULTS & DISCUSSION:Intravenous FR-?-targeted HDL resulted in high uptake of the fluorescent nanoparticle in host liver and spleen. The ip. injection of fluorescent HDL produced moderate fluorescence throughout the abdomen. Conversely, animals receiving the ip. FR-?-targeted HDL showed a high fluorescence signal in ovarian tumors, surpassing that seen in all of the host tissues. CONCLUSION:The authors' findings demonstrate that the combination of local-regional ip. administration and FR-?-directed nanoparticles provides an enhanced approach to selectively targeting ovarian cancer cells for drug treatment.

SUBMITTER: Corbin IR

PROVIDER: S-EPMC3652907 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Near-infrared fluorescent imaging of metastatic ovarian cancer using folate receptor-targeted high-density lipoprotein nanocarriers.

Corbin Ian R IR Ng Kenneth K KK Ding Lili L Jurisicova Andrea A Zheng Gang G

Nanomedicine (London, England) 20121015 6

<h4>Aim</h4>The targeting efficiency of folate receptor-α (FR-α)-targeted high-density lipoprotein nanoparticles (HDL NPs) was evaluated in a syngeneic mouse model of ovarian cancer.<h4>Materials & methods</h4>Folic acid was conjugated to the surface of fluorescent-labeled HDL NPs. In vivo tumor targeting of folic acid-HDL NPs and HDL NPs were evaluated in mice with metastatic ovarian cancer following intravenous or intraperitoneal (ip.) administration.<h4>Results & discussion</h4>Intravenous FR ...[more]

PMID: 23067398

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Project description:BACKGROUND:To meet clinical needs, fluorescence-guided surgery has emerged as a new technique that guides surgeons in the resection of cancerous tissue by highlighting tumour lesions during surgery. We aimed to evaluate the novel ovarian cancer-specific antibody fluorescent probe COC183B2-800 (COC183B2 conjugated with IRDye800CW) in tumour-specific imaging to determine if it can help surgeons remove malignant lesions under fluorescence guidance. METHODS:The expression of OC183B2 antigen in epithelial ovarian cancer (EOC) tissues and cell lines was determined using immunohistochemistry (IHC). Western blotting was used to verify the expression of OC183B2 in SKOV3-Luc tumours. Antibodies against OC183B2 and mouse immunoglobulin G1 (IgG1) were conjugated with IRDye800CW to develop the antibody fluorescent probes COC183B2-800 and IgG-800 (immunoglobulin G1 conjugated with IRDye800CW). A subcutaneous mouse tumour model of SKOV3-Luc cells was constructed. Bioluminescent imaging (BLI) was conducted to detect the tumour location. Near-infrared fluorescence (NIRF) imaging was performed after the mice were injected with imaging agents. The mice were sacrificed 96?h postinjection, and the biodistribution assays were performed using NIRF imaging. RESULTS:In 69 EOC patients, the total positive rate of OC183B2 in EOC tissues was 89.9% (62/69). Expression of the OC183B2 antigen was positive in SKOV3-Luc, 3AO, ES2 and A2780 cells. The OC183B2 antigen could be detected in SKOV3-Luc tumours. NIRF imaging of the COC183B2-800 probe at different doses showed a high fluorescent signal at the tumour location that was in line with the site detected by bioluminescent imaging. The tumour background ratio (TBR) was significantly higher in the COC183B2-800 group than in the IgG-800, IRDye800CW and PBS groups. The fluorescent probe COC183B2-800 is metabolized mainly through the liver and does not accumulate in other organs. CONCLUSIONS:COC183B2-800 shows effective tumour-specific targeting of EOC and is a promising diagnostic and therapeutic tool for fluorescence-guided surgery.

Dataset Information

Near-infrared fluorescent imaging of metastatic ovarian cancer using folate receptor-targeted high-density lipoprotein nanocarriers.

Publications

Near-infrared fluorescent imaging of metastatic ovarian cancer using folate receptor-targeted high-density lipoprotein nanocarriers.

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