Developing high throughput cancer biomarker monitoring platform has been a long demand in cancer research. It can enable early diagnosis and help tracking recurrence of disease which will eventually increase patient’s survival rate without deteriorating quality of patient’s life. This will help doctors selectively treat patients and utilize precision medicine Most cancer biomarker monitoring studies take following two approaches; invasive and non-invasive method. First requires introduction of functionalized nanoparticles with an invasive way such as needle injection. It is designed to perform in vivo experiment where nanoparticles circulate in the body and target specific cancer cells of interest. Current obstacles in biomedical imaging for in vivo cancer diagnosis is the synthesis of hydrophilic Quantum Dots (QDs) with emission wavelength in the near-IR, a high quantum yield, stability in water, and relatively small sizes. The optimum wavelength for in vivo optical imaging, taking into account the absorbance from melanin in the epidermis, hemoglobin in blood, and water in tissue, is in the range of 700-900 nm. In this study, we successfully synthesized NIR-QDs that meets all these requirements for in vivo optical imaging. NIR QDs with emission wavelength > 700 nm, 60% QY, and high stability. High quantum yield was maintained for about 100 hours in water. We also studied circulation and retention of QDs in vivo. Fluorescent images showed that after 5 minutes of tail vein injection, QDs traveled throughout whole body and even big veins were easily visible. High fluorescence was maintained up to 100 minutes post injection (p.i.). NIR-QDs mostly cleared out by urine and feces and only 10% accumulated in RES system (especially in liver and spleen) after 24 hours p.i.
Non-invasive method is also widely studied because it is more patient friendly, does not require a large amount of tumor tissue, and enables regular monitoring. Targeting cancer specific biomarkers from a collection of patients’ bodily fluids such as urine and blood is actively investigated. For example, about 10 million men take a serum prostate specific antigen (PSA) test for prostate cancer, the second leading cause of cancer death in men in the USA. Due to its high controversy, alternate test methods are developed, including testing genomic biomarkers such as PCA3 and fusion genes. Identifying genetic diversity is important as it can provide insights on disease progression and treatment. In our study, we have tested a panel of prostate cancer genetic biomarkers (AMACR, PCA3, PSMA, TMPRSS2-ERG fusion genes) with oligonucleotide sandwich assay using gold nanoparticles (AuNPs). We established high sensitivity and throughput by controlling oligos conjugated to AuNPs. Using this in vitro test, patient urine samples are tested to find correlation between expression of panel of genetic biomarkers and clinical outcomes. We found that patients with same Gleason score and PSA result showed different TMPRSS2-ERG fusion gene expressions. This indicates that oligonucleotide sandwich assay can provide a very important insight on disease progression that conventional tests could not
