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Updated: Jan 1, 2026
Nanosensors to Detect Protease Activity In Vivo for Noninvasive Diagnostics
Published on: July 16, 2018
A nanometer-sized protease inhibitor for precise cancer diagnosis and treatment
Ping Hu1, Le Shang, Jincan Chen
1State Key Laboratory of Structural Chemistry, and CAS Key Laboratory of Design and Assembly of Functional Nanostructures, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, Fujian 350002, China. xupeng@fjirsm.ac.cn zchen@fjirsm.ac.cn.
Abstract:
Inhibition of pro-cancer proteases is a potent anticancer strategy. However, protease inhibitors are mostly developed in the forms of small molecules or peptides, which normally suffer from insufficient metabolic stability. The fast clearance significantly impairs the antitumor effects of these inhibitors. In this study, we report a nanometer-sized inhibitor of a pro-cancer protease, suppressor of tumorigenicity 14 (st14), which has been reported as a potent prognostic marker for multiple cancers. This st14 inhibitor was fabricated by conjugating a recombinant st14 inhibitor (KD1) with carbon quantum dots (CQDs). CQD-KD1 not only demonstrated high potency of inhibiting st14 activity in biochemical experiments, but also remarkably suppressed the invasion of breast cancer cells. In contrast to the original recombinant KD1, CQD-KD1 demonstrated a prolonged retention time in plasma and at the tumor site because of the reduced renal clearance. Consistently, CQD-KD1 demonstrated enhanced efficacies of suppressing tumor growth and cancer metastases in vivo. In addition, CQD-KD1 precisely imaged tumor tissues in cancer-grafted mice by specifically targeting the over-expressed st14 on the tumor cell surface, which indicates CQD-KD1 as a potent probe for the fluorescence guided surgery of tumor resection. In conclusion, this study demonstrates that CQD-KD1 is a highly potent diagnostic and therapeutic agent for cancer treatments.
Insights
A novel nanometer-sized inhibitor, CQD-KD1, effectively targets the pro-cancer protease suppressor of tumorigenicity 14 (st14). This enhanced inhibitor improves stability and efficacy for cancer diagnosis and treatment.
Area of Science:
- Biotechnology
- Nanomedicine
- Cancer Research
Background:
- Protease inhibitors are crucial anticancer agents but often lack metabolic stability.
- Small molecule and peptide inhibitors face rapid clearance, limiting their therapeutic potential.
- Suppressor of tumorigenicity 14 (st14) is a pro-cancer protease and a prognostic marker in multiple cancers.
Purpose of the Study:
- To develop a nanometer-sized inhibitor for the pro-cancer protease st14.
- To enhance the metabolic stability and antitumor efficacy of a recombinant st14 inhibitor (KD1).
- To evaluate the diagnostic and therapeutic potential of the novel nanomedicine.
Main Methods:
- Fabrication of a nanometer-sized inhibitor (CQD-KD1) by conjugating KD1 with carbon quantum dots (CQDs).
- In vitro assessment of st14 inhibition and breast cancer cell invasion.
- In vivo evaluation of pharmacokinetic properties, tumor growth suppression, and metastasis inhibition in mice.
- In vivo fluorescence imaging for tumor targeting and guided surgery.
Main Results:
- CQD-KD1 exhibited high potency in inhibiting st14 activity and suppressing breast cancer cell invasion.
- CQD-KD1 demonstrated prolonged retention in plasma and at tumor sites due to reduced renal clearance.
- Enhanced in vivo efficacy in suppressing tumor growth and metastasis was observed.
- Precise imaging of tumor tissues was achieved, highlighting potential for fluorescence-guided surgery.
Conclusions:
- CQD-KD1 represents a significant advancement in developing stable and effective protease inhibitors for cancer therapy.
- The nanomedicine shows promise as a dual-action agent for both diagnosis and therapy.
- This study validates CQD-KD1 as a potent tool for cancer treatment and surgical guidance.
