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Updated: Sep 14, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
A novel nanomissile targeting two biomarkers and accurately bombing CTCs with doxorubicin
Yu Gao1, Xiaodong Xie, Fengqiao Li
1Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, and Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou 350108, China. pharmlink@gmail.com cmapcjia1234@163.com.
Abstract:
Rare circulating tumor cells (CTCs) cause >50% of primary colorectal cancer survivors to develop deadly metastasis at 3-5 years after surgery; the current chemotherapies can do nothing about these cells. Herein, we synthesized a novel doxorubicin (DOX)-entrapped mesoporous silica nanoparticle (MSN), covalently-conjugated with two aptamers, for simultaneously targeting EpCAM and CD44, the typical surface biomarkers of colorectal CTCs. The nanomissile can specifically capture the metastasis-prone CTCs spiked in healthy human blood in a competitive-binding manner. The binding not only accurately delivers DOX into the cancer cells via the biomarker-mediated endocytosis to inhibit CTC viability through the DOX-dependent mechanism, but also inhibits the adhesion of cancer cells to the endothelium and the consequent transmembrane migration through the DOX-independent mechanism. The molecular entity of the conjugate and its pharmaceutical DOX encapsulation-releasing capacity are well-demonstrated via various physiochemical characterizations including gel electrophoresis, which proves the >8-hour biostability of the nanomissile in blood, long enough for it to chase CTCs in mice and synergistically inhibit the CTC-induced lung metastasis more potently than its single aptamer-conjugated counterparts and DOX itself. The present strategy may pave a new avenue for safe and effective cancer metastasis chemoprevention.
Insights
This study developed a novel nanoparticle drug delivery system for colorectal cancer. The dual-aptamer-conjugated nanomissile targets circulating tumor cells (CTCs), delivering doxorubicin (DOX) to inhibit metastasis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Colorectal cancer (CRC) survivors face high metastasis risk from circulating tumor cells (CTCs).
- Current chemotherapies are ineffective against these metastasis-prone CTCs.
- Targeting specific biomarkers on CTCs is crucial for effective treatment.
Purpose of the Study:
- To develop a novel nanoparticle system for targeting and eliminating metastasis-prone colorectal CTCs.
- To investigate the efficacy of dual aptamer-conjugated nanoparticles in inhibiting CTC adhesion and migration.
- To evaluate the potential of this strategy for cancer metastasis chemoprevention.
Main Methods:
- Synthesis of doxorubicin (DOX)-entrapped mesoporous silica nanoparticles (MSNs) conjugated with EpCAM and CD44 aptamers.
- In vitro capture of spiked CTCs from human blood using the dual-aptamer MSN system.
- Assessment of DOX-mediated cytotoxicity and DOX-independent inhibition of cell adhesion and migration.
- In vivo evaluation of nanoparticle biostability, biodistribution, and anti-metastasis efficacy in a mouse model.
Main Results:
- The dual-aptamer MSN effectively captured colorectal CTCs in a competitive binding manner.
- Biomarker-mediated endocytosis delivered DOX, inhibiting CTC viability.
- DOX-independent mechanisms reduced cancer cell adhesion and transmigration.
- The nanomissile demonstrated >8-hour blood biostability and superior inhibition of lung metastasis in mice compared to controls.
Conclusions:
- The novel dual-aptamer MSN system offers a promising strategy for targeting and eliminating metastasis-prone CTCs.
- This approach provides a dual mechanism of action, inhibiting both CTC viability and metastasis.
- The developed nanomissile shows potential for effective cancer metastasis chemoprevention with improved safety and efficacy.
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