Blood-brain barrier and blood-brain tumor barrier penetrating peptide-drug conjugate as targeted therapy for the treatment of lung cancer brain metastasis.

in Lung cancer (Amsterdam, Netherlands) by Meng-Zhu Zheng, Zhan-Qun Yang, Sun-Li Cai, Li-Ting Zheng, Yuan Xue, Long Chen, Jian Lin

TLDR

  • The study found a way to get drugs into the brain to treat a type of cancer that often spreads to the brain. The study used a special peptide that can cross the barrier that keeps drugs out of the brain. The peptide was attached to a drug called paclitaxel, which killed the cancer cells in the brain. The study showed that the peptide-drug combination was effective in treating the cancer in mice. This study suggests that this combination could be used to treat lung cancer brain metastasis in humans, but more research is needed to make sure it's safe and effective.

Abstract

Lung cancer is the leading cause of cancer deaths worldwide. Brain metastasis of lung cancer, which counts for nearly 50% of late-stage lung cancer patients, is a sign of a really poor prognosis. However, the presence of blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) limits the penetration of drugs from the blood into the brain and thus restricts their accumulation in brain tumors. Systematic delivery of drugs into brain and brain tumor lesion using BBB and BBTB penetrating vehicles represents a promising strategy to overcome the BBB and BBTB limitations. Hence, we validated one of our previously identified BBB/BBTB penetrating peptide and its drug conjugate form for the treatment of lung cancer brain metastasis. With in vitro experiment, we first validated that the receptor LRP1, which mediated the peptide penetration of the BBB, was expressed on lung cancer cells and thus can be targeted by the peptide to overcome BBTB. With this delivery peptide, we constructed peptide-paclitaxel conjugate (the PDC) and in vitro validation showed that the PDC can across the BBB and efficiently kill lung cancer cells. We therefore constructed mouse lung cancer brain metastasis xenograft. In vivo anti-tumor validations showed that the PDC efficiently inhibited the proliferation of the brain resident lung cancer cells and significantly expanded the survival of the mouse xenograft, with no visible damages to the organs. Overall, our study provided potential therapeutic drugs for the treatment of lung cancer brain metastasis that may be clinically effective in the near future.

Overview

  • The study aims to validate a previously identified BBB/BBTB penetrating peptide and its drug conjugate form for the treatment of lung cancer brain metastasis. The methodology used for the experiment includes in vitro and in vivo validations. The primary objective of the study is to demonstrate the potential therapeutic drugs for the treatment of lung cancer brain metastasis that may be clinically effective in the near future.

Comparative Analysis & Findings

  • The study showed that the peptide-paclitaxel conjugate (PDC) can cross the BBB and efficiently kill lung cancer cells. In vivo anti-tumor validations showed that the PDC efficiently inhibited the proliferation of the brain resident lung cancer cells and significantly expanded the survival of the mouse xenograft, with no visible damages to the organs.

Implications and Future Directions

  • The study's findings suggest that the PDC may be a promising therapeutic drug for the treatment of lung cancer brain metastasis. However, further studies are needed to evaluate the safety and efficacy of the PDC in clinical trials. Additionally, the study highlights the potential of using BBB/BBTB penetrating peptides as drug delivery vehicles for the treatment of brain tumors.
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