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Lipid-polymer hybrid nanoparticles: A photoacoustic imaging tool for ovarian cancer diagnosis

  • Author(s): Chen, Chien-Ju
  • Advisor(s): Jokerst, Jesse V
  • et al.
Abstract

The survival rate of patients with ovarian cancer is over 90% in Stages I and II but detection strategies based on CA125 testing are ineffective. Hence, this screening approach not only fails to decrease ovarian cancer mortality but also causes significant harm including major surgery in cancer free women. Fortunately, the metrics of ultrasound-based techniques are encouraging—a recent large scale trial of over 200,000 women indicated that the sensitivity and specificity were 89.4% and 99.8%, respectively, when combined with CA125 tests. However, the positive predictive value of ovarian cancer was only 43.3%. Therefore, we hypothesize that using photoacoustic ultrasound

combined with lipid-polymer hybrid nanoparticles can achieve advances in specificity and sensitivity that are need in population-wide studies. In our study, we used poly-lacticco- glutamic acid (PLGA), lecithin, and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate(polyethylene glycol)]-5000 (DSPE-PEG-folate) to fabricate hybrid nanoparticles. The photoacoustic imaging agents DiR or IR-1061 were encapsulated in PLGA hydrophobic core. The folate-functionalized nanoparticles can actively target HeLa cells which overexpress folate receptors on their cell membrane. The main hypothesis is that the folate-functionalized nanoparticles could produce higher

contrast between ovarian cancer tissues and normal tissues than nanoparticles without folate modification. Also, we proved our IR-1061-loaded nanoparticles had a pH-responsive release profile. We can even use photoacoustic imaging to track the releasing

IR-1061 in PBS at different pH values. In the future, we attempt to conjugate IR-1061 molecules with anti-cancer drugs to endow our nanoparticles theranostic capability. Our long-term goal is to achieve in vivo photoacoustic imaging and theranostic treatment of ovarian cancer patients.

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