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Targeting self-assembly peptide for inhibiting breast tumor progression and metastasis
Shi Luo1, Jiaxing Feng1, Linyu Xiao1
1Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
Abstract:
The ubiquitous interactions between tumor cells and the surrounding microenvironment contribute to tumor metastasis, interrupting these communications has, therefore, a great potential for antimetastasis therapy. Here, we describe an in situ self-assembly strategy that limits direct contact between tumor cells and the tumor microenvironment (TME). In this strategy, the Lys-Leu-Val-Phe-Phe (KLVFF) peptide motifs are targeted to the tumor by hyaluronic acid (HA) functionalized liposomes and spontaneously undergo self-assembly to form nanofibers with a net-like structure wrapping around tumor cells. The fibrous nanostructures bury the membrane protrusions and thus hinder the migration and invasion of tumor cells, especially the transmigration through the fenestrated endothelium. The nanofibril coatings on tumor cells significantly block tumor cells induced platelet aggregation in vitro and prevent the adhesion of platelet around circulating tumor cells (CTCs) in vivo, thus limit the pro-metastasis effect of platelets and prevent the early metastasis. Furthermore, the nano-nets stably retain in the primary tumor site for over 72 h and effectively prevent the activation of intratumoral platelet, which suppress tumor progression and the spontaneous lung metastasis in 4T1 breast cancer mice model. Our study paves a promising avenue to combat tumor metastasis by regulating the interactions between tumor cells and the TME.
Insights
This study introduces a novel self-assembly nanofiber strategy to block tumor cell interactions with their microenvironment, significantly inhibiting metastasis and tumor progression in a mouse model.
Area of Science:
- Biomaterials Science
- Cancer Biology
- Nanotechnology
Background:
- Tumor cell interactions with the microenvironment drive metastasis.
- Targeting these interactions offers a therapeutic strategy against cancer spread.
Purpose of the Study:
- To develop an in situ self-assembly strategy using peptide nanofibers to limit tumor cell-microenvironment contact.
- To investigate the anti-metastasis potential of this nanofiber system.
Main Methods:
- Hyaluronic acid (HA)-functionalized liposomes delivering Lys-Leu-Val-Phe-Phe (KLVFF) peptides were used for tumor targeting.
- Self-assembled nanofibers formed a net-like structure around tumor cells.
- In vitro and in vivo studies assessed the impact on tumor cell migration, invasion, and platelet interactions.
Main Results:
- The nanofiber 'nano-nets' hindered tumor cell migration and invasion, including transmigration through endothelium.
- Nanofibril coatings prevented tumor cell-induced platelet aggregation and adhesion of platelets to circulating tumor cells (CTCs).
- The nano-nets suppressed primary tumor progression and lung metastasis in a 4T1 breast cancer mouse model over 72 hours.
Conclusions:
- In situ self-assembling nanofibers effectively block tumor cell-TME interactions, offering a promising anti-metastasis therapy.
- This approach limits platelet-mediated pro-metastasis effects and suppresses tumor growth and spread.
