Related Experiment Video
Updated: Aug 28, 2025
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Site-Specific Polyplex on CCR7 Down-Regulation and T Cell Elevation for Lymphatic Metastasis Blocking on Breast
Yueyang Deng1, Caixia Tan1, Shuguang Huang1
1NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, China.
Abstract:
Tumor metastasis contributes to high cancer mortality. Tumor cells in lymph nodes (LNs) are difficult to eliminate but underlie uncontrollable systemic metastasis. The CC chemokine receptor 7 (CCR7) is overexpressed in tumor cells and interacts with CC chemokine ligand 21 (CCL21) secreted from LNs, potentiating their lymphatic migration. Here, a site-specific polyplex is developed to block the CCR7-CCL21 signal and kill tumor cells toward LNs, greatly limiting their lymphatic infiltration. A CCR7-targeting small interfering RNA (siCCR7) is condensed by mPEG-poly-(lysine) with chlorin e6 (Ce6) modification (PPLC) to form PPLC/siCCR7. The knockdown of CCR7 by siCCR7 in tumor cells significantly reduced their response on CCL21 and LN tropism. Additionally, photodynamic therapy-mediated immune activation precisely targets and kills tumor cells released from the primary foci before they reaches the LNs, reducing the number of tumor cells entering the LNs. Consequently, the PPLC/siCCR7 polyplexes inhibited up to 92% of lung metastasis in 4T1 tumor bearing mice and reduced tumor cell migration to LNs by up to 80%. This site-specific strategy optimized anti-metastasis efficacy and promotes the clinical translational development of anti-metastatic therapy.
Insights
This study developed a novel polyplex to block tumor cell migration to lymph nodes (LNs) and kill metastatic cells. The therapy significantly reduced lung metastasis and LN infiltration in mice, offering a promising anti-metastasis strategy.
Area of Science:
- Oncology
- Nanomedicine
- Immunotherapy
Background:
- Tumor metastasis, particularly to lymph nodes (LNs), is a major cause of cancer mortality.
- The CC chemokine receptor 7 (CCR7) and its ligand CCL21 axis drives tumor cell lymphatic migration and subsequent metastasis.
- Effective strategies are needed to prevent tumor cell infiltration into LNs.
Purpose of the Study:
- To develop a site-specific polyplex to block the CCR7-CCL21 signaling pathway.
- To simultaneously eliminate tumor cells migrating towards LNs.
- To reduce lymphatic metastasis and improve anti-cancer therapy.
Main Methods:
- A polyplex (PPLC/siCCR7) was engineered, condensing CCR7-targeting small interfering RNA (siCCR7) with mPEG-poly-(lysine) and chlorin e6 (Ce6).
- siCCR7 was used to knock down CCR7 expression in tumor cells, reducing their response to CCL21.
- Photodynamic therapy (PDT) was employed for immune activation and targeted tumor cell killing.
Main Results:
- siCCR7 knockdown significantly reduced tumor cell tropism towards CCL21 and LNs.
- The PPLC/siCCR7 polyplexes inhibited lung metastasis by up to 92% in a mouse model.
- Tumor cell migration to LNs was reduced by up to 80% using this targeted approach.
Conclusions:
- The developed site-specific polyplex effectively inhibits tumor cell lymphatic infiltration and metastasis.
- This strategy combines targeted gene silencing with photodynamic therapy for enhanced anti-metastasis efficacy.
- The approach shows significant potential for clinical translation in anti-metastatic therapies.
