Bo Sun

Quantitative Detection of Serum Protein-Specific Glycosylation in Ovarian Cancer Based on a Signal-Convertible Mass-Tagged Probe Set

The aberrant expression of sialic acid (Sia) on the surface of serum CA125 protein (CA125-Sia) is closely related to the occurrence of ovarian cancer and may have potential utility for early detection of ovrian cancer. However, the accurate determination of protein-specific glycosylation profiles poses significant analytical challenges, primarily due to the need for simultaneous identification of the target protein and quantification of specific glycosylation as well as their low levels in the early stages of certain diseases. Herein, we report a signal-convertible mass-tagged probe set system for the mass spectrometric detection of serum CA125-Sia. This probe set consists of three functional probes: a capture probe (CP), a labeling probe (LP), and a mass-tagged probe (MP). The serum CA125 protein was first captured by CP, and the terminal Sia was labeled by LP with the help of a heterobifunctional cross-linker. Then, the MP can hybridize with the LP attached to the Sia. Once the hybridization was formed, the MP in the hybridization was hydrolyzed into small fragments in the presence of exonuclease III (Exo III), while the LP reverted to a single-stranded state and could continuously perform the cycle process of hybridization and hydrolysis, thus realizing signal amplification. This strategy has been successfully used to quantify CA125-Sia in serum. It provides a promising platform for the quantification of protein-specific glycoforms in serum samples. Our findings suggest that CA125-Sia may be a novel potential diagnostic marker for the early detection of ovarian cancer.

PLGA‐PEG‐c(RGDfK)‐ Kushenol E Micelles With a Therapeutic Potential for Targeting Ovarian Cancer

Background: As a naturally derived inhibitor of autophagy, Kushenol E (KE) is a biprenylated flavonoid and is isolated from Sophora flavescens , which has been used for the treatment of cancer, hepatitis, and skin diseases. However, KE, as a poorly soluble drug, exhibited strong autophagy regulating activity in in vitro cancer cell lines, but no related studies have reported its antiovarian cancer property. Therefore, it is very beneficial to enhance the antineoplastic properties of KE by establishing an ovarian tumor‐targeting nanoparticle system modified with tumor‐homing c(RGDfK) peptides. Materials and Methods: In the current study, poly(lactic‐co‐glycolic acid)‐poly(ethylene glycol)‐modified with cyclic RGDfK peptide (PLGA‐PEG‐c(RGDfK))‐KE micelles (PPCKM) were prepared to overcome the poor water solubility of KE to meet the requirement of tumor‐active targeting. The effect of PPCKM on ovarian cancer was evaluated on SKOV‐3 cells and xenograft models in BALB/c nude mice. Results: The PPCKM showed a higher drug cumulative release ratio (82.16 ± 7.69% vs. 34.96 ± 3.05%, at 1.5 h) with good morphology, particle size (93.41 ± 2.84 nm), and entrapment efficiency (89.7% ± 1.3%). The cell viability, migration, and apoptosis analysis of SKOV‐3 cells demonstrated that PPCKM retained potent antitumor effects and promoted apoptosis at early and advanced stages with concentration‐dependent. Based on the establishment of xenograft models in BALB/c nude mice, we discovered that PPCKM reduced tumor volume and weight, inhibited proliferating cell nuclear antigen (PCNA) and Ki67 expression, as well as promoted apoptosis by targeting the tumor site. Conclusion: The findings in this study suggest that PPCKM may serve as an effective therapeutic option for ovarian cancer.