Detection and Analysis of Tumor Fluorescence Using a Two-Photon Optical Fiber Probe

Thomas, Thommey P.; Myaing, Mon Thiri; Ye, Jing Yong; Candido, Kimberly A.; Kotlyar, Alina; Beals, John M.; Cao, Peter; Keszler, B.; Patri, Anil K.; Norris, Theodore B.; Baker, James R.

doi:10.1529/biophysj.103.034462

Cited by 70 publications

(74 citation statements)

References 30 publications

(30 reference statements)

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“…2C). Previously, we have obtained similar results while demonstrating targeting to tumor cells using a two-photon optical fiber probe for the detection of fluorescence (28).…”

Section: Resultssupporting

confidence: 73%

Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer

Kukowska-Latallo¹,

Candido²,

Cao³

et al. 2005

Cancer Research

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832

688

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Prior studies suggested that nanoparticle drug delivery might improve the therapeutic response to anticancer drugs and allow the simultaneous monitoring of drug uptake by tumors. We employed modified PAMAM dendritic polymers <5 nm in diameter as carriers. Acetylated dendrimers were conjugated to folic acid as a targeting agent and then coupled to either methotrexate or tritium and either fluorescein or 6-carboxytetramethylrhodamine. These conjugates were injected i.v. into immunodeficient mice bearing human KB tumors that overexpress the folic acid receptor. In contrast to nontargeted polymer, folate-conjugated nanoparticles concentrated in the tumor and liver tissue over 4 days after administration. The tumor tissue localization of the folate-targeted polymer could be attenuated by prior i.v. injection of free folic acid. Confocal microscopy confirmed the internalization of the drug conjugates into the tumor cells. Targeting methotrexate increased its antitumor activity and markedly decreased its toxicity, allowing therapeutic responses not possible with a free drug. (Cancer Res 2005; 65(12): 5317-24 )

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“…2C). Previously, we have obtained similar results while demonstrating targeting to tumor cells using a two-photon optical fiber probe for the detection of fluorescence (28).…”

Section: Resultssupporting

confidence: 73%

Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer

Kukowska-Latallo¹,

Candido²,

Cao³

et al. 2005

Cancer Research

Self Cite

832

688

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“…Dye-functionalized dendrimers offer many opportunities for imaging purposes [37]. The purity and homogeneity of the dye-functionalized PAMAM dendrimers are important for their biological performance [29].…”

Section: Resultsmentioning

confidence: 99%

“…Polyanionic PAMAM-SAH dendrimers were synthesized and characterized according to our previous literature procedures [23]. 6T-labeled G5 dendrimers with succinamic acid surfaces were prepared according to a reported procedure with slight modification [37]. Instead of a final acetylation of the remaining amines of G5 dendrimers, a carboxylation using succinic anhydride was performed to convert the remaining amines of the G5 dendrimers to the succinamic acid groups, according to our previous report [6,23].…”

Section: Methodsmentioning

confidence: 99%

CE of poly(amidoamine) succinamic acid dendrimers using a poly(vinyl alcohol)‐coated capillary

2008

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Various generations (G1-G8) of negatively charged poly(amidoamine) (PAMAM) succinamic acid dendrimers (PAMAM-SAH) were analyzed by CE using a poly(vinyl alcohol)-coated capillary. Due to its excellent stability and osmotic flow-shielding effect, highly reproducible migration times were achieved for all generations of dendrimer (e.g., RSD for the migration times of G5 dendrimer was 0.6%). We also observed a reverse trend in migration times for the PAMAM-SAH dendrimers (i.e., higher generations migrated faster than lower generation dendrimers) compared to amine-terminated PAMAM dendrimers reported in the literature. This reversal in migration times was attributed to the difference in counterion binding around these negatively charged dendrimers. This reverse trend allowed a generational separation for lower generation (G1-G3) dendrimers. However, a sufficient resolution for the migration peaks of higher generations (G4-G5) in a mixture could not be achieved. This could be due to their nearly identical charge/mass ratio and dense molecular conformations. In addition, we show that dye-functionalized PAMAM-SAH dendrimers can also be analyzed with high reproducibility using this method.

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“…21,22 Using a double-clad fiber ͑DCF͒ as the probe, we demonstrated more than one order of magnitude increase in the detected two-photon excited fluorescence signals. [23][24][25] Here, we demonstrate the use of this DCF-TPOFF probe to conduct two-wavelength-channel cell detection, first in whole blood in vitro, and subsequently in vivo.…”

Section: Introductionmentioning

confidence: 90%

Fiber-optic multiphoton flow cytometry in whole blood and in vivo

Chang

Thomas

et al. 2010

J. Biomed. Opt.

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Abstract. Circulating tumor cells in the bloodstream are sensitive indicators for metastasis and disease prognosis. Circulating cells have usually been monitored via extraction from blood, and more recently in vivo using freespace optics; however, long-term intravital monitoring of rare circulating cells remains a major challenge. We demonstrate the application of a two-photon-fluorescence optical fiber probe for the detection of cells in whole blood and in vivo. A double-clad fiber was used to enhance the detection sensitivity. Two-channel detection was employed to enable simultaneous measurement of multiple fluorescent markers. Because the fiber probe circumvents scattering and absorption from whole blood, the detected signal strength from fluorescent cells was found to be similar in phosphate-buffered saline ͑PBS͒ and in whole blood. The detection efficiency of cells labeled with the membrane-binding dye 1,1Ј-dioctadecyl-3,3,3Ј ,3Ј-tetramethylindoldicarbocyanine, 4-chlorobenzenesulfonate ͑DiD͒ was demonstrated to be the same in PBS and in whole blood. A high detection efficiency of green fluorescent protein ͑GFP͒-expressing cells in whole blood was also demonstrated. To characterize in vivo detection, DiDlabeled untransfected and GFP-transfected cells were injected into live mice, and the cell circulation dynamics was monitored in real time. The detection efficiency of GFP-expressing cells in vivo was consistent with that observed ex vivo in whole blood.

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Detection and Analysis of Tumor Fluorescence Using a Two-Photon Optical Fiber Probe

Cited by 70 publications

References 30 publications

Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer

Nanoparticle Targeting of Anticancer Drug Improves Therapeutic Response in Animal Model of Human Epithelial Cancer

CE of poly(amidoamine) succinamic acid dendrimers using a poly(vinyl alcohol)‐coated capillary

Fiber-optic multiphoton flow cytometry in whole blood and in vivo

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