Targeted Delivery of Chemo-Sonodynamic Therapy via Brain Targeting, Glutathione-Consumable Polymeric Nanoparticles for Effective Brain Cancer Treatment.

in Advanced science (Weinheim, Baden-Wurttemberg, Germany) by Haoan Wu, Xingchun Gao, Yuanyuan Luo, Jiang Yu, Gretchen Long, Zhaozhong Jiang, Jiangbing Zhou

TLDR

  • The study is about creating tiny particles called nanoparticles that can help treat a type of brain tumor called glioblastoma. The nanoparticles are made using a special type of polymer and are designed to shrink and be delivered to the brain. They also carry a drug called doxorubicin and a light-sensitive compound called chlorin e6. When the nanoparticles reach the brain and the light is shone on them, the drug and light work together to kill the tumor cells. The study shows that the nanoparticles are effective at killing the tumor cells and may be a new way to treat glioblastoma.

Abstract

Glioblastoma (GBM) is the most aggressive tumor of the central nervous system and remains universally lethal due to lack of effective treatment options and their inefficient delivery to the brain. Here the development of multifunctional polymeric nanoparticles (NPs) for effective treatment of GBM is reported. The NPs are synthesized using a novel glutathione (GSH)-reactive poly (2,2″-thiodiethylene 3,3″-dithiodipropionate) (PTD) polymer and engineered for brain penetration through neutrophil elastase-triggered shrinkability, iRGD-mediated targeted delivery, and lexiscan-induced autocatalysis. It is found that the resulting lexiscan-loaded, iRGD-conjugated, shrinkable PTD NPs, or LiPTD NPs, efficiently penetrate brain tumors with high specificity after intravenous administration. Furthermore, it is demonstrated that LiPTD NPs are capable of efficient encapsulation and delivery of chemotherapy doxorubicin and sonosensitizer chlorin e6 to achieve combined chemotherapy and sonodynamic therapy (SDT). It is demonstrated that the capability of GSH depletion of LiPTD NPs further augments the tumor cell killing effect triggered by SDT. As a result, treatment with LiPTD NPs effectively inhibits tumor growth and prolongs the survival of tumor-bearing mice. This study may suggest a potential new approach for effective GBM treatment.

Overview

  • The study focuses on the development of multifunctional polymeric nanoparticles (NPs) for effective treatment of GBM. The NPs are synthesized using a novel glutathione (GSH)-reactive poly (2,2″-thiodiethylene 3,3″-dithiodipropionate) (PTD) polymer and engineered for brain penetration through neutrophil elastase-triggered shrinkability, iRGD-mediated targeted delivery, and lexiscan-induced autocatalysis. The primary objective of the study is to demonstrate the efficient penetration and delivery of lexiscan-loaded, iRGD-conjugated, shrinkable PTD NPs to brain tumors and their capability to enhance the tumor cell killing effect triggered by sonodynamic therapy (SDT).

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The results show that the lexiscan-loaded, iRGD-conjugated, shrinkable PTD NPs efficiently penetrate brain tumors with high specificity after intravenous administration. The study also demonstrates that LiPTD NPs are capable of efficient encapsulation and delivery of chemotherapy doxorubicin and sonosensitizer chlorin e6 to achieve combined chemotherapy and sonodynamic therapy (SDT). The capability of GSH depletion of LiPTD NPs further augments the tumor cell killing effect triggered by SDT. The key findings of the study suggest that the lexiscan-loaded, iRGD-conjugated, shrinkable PTD NPs are a potential new approach for effective GBM treatment.

Implications and Future Directions

  • The study's findings suggest the potential impact on the field of research or clinical practice. The development of multifunctional polymeric nanoparticles (NPs) for effective treatment of GBM is a promising approach. The study identifies the limitations of the study that need to be addressed in future research, such as the need for further preclinical studies to evaluate the safety and efficacy of LiPTD NPs in humans. The study suggests possible future research directions that could build on the results of the study, explore unresolved questions, or utilize novel approaches, such as the development of LiPTD NPs with different chemotherapy drugs or sonosensitizers, or the evaluation of LiPTD NPs in combination with other therapies.
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