Chinese researchers build an ‘aircraft carrier’

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Cancer is a leading cause of death globally, accounting for around 10 million deaths annually. The most common type of cancer is breast cancer, which saw 2.26 million new cases in 2020 and led to 685,000 deaths globally.

Cancer arises from the transformation of normal cells into tumor cells in a multi-stage process that generally progresses from a precancerous lesion to a malignant tumor. The cancer then sometimes metastasizes, meaning it spreads from one part of the body to another. This usually means that the cancer has advanced and reached a stage where it requires more aggressive treatment.

Conventional treatment methods like surgery, radiation therapy, and chemotherapy can sometimes eradicate cancer cells but it leads to the degeneration of healthy tissues.

Researchers from China say they have a solution that can not only inhibit the growth of the primary tumors but also the tumors that have metastasized, as first reported by the South China Morning Post (SCMP).

The team has developed an intelligent nanoplatform that can simultaneously target multiple factors associated with tumor growth and metastasis, especially helpful in the treatment of breast cancer. Many cancers can be cured if detected early and treated effectively.

The nanoplatform is called an ‘aircraft carrier,’ as each particle performs a unique task. The researchers used a polymer as a deck and modified its surface with targeting agent LyP-1 peptide, which can selectively bind to breast cancer cells and induce cell death. This helps the nano platform to navigate and find the tumors, which the team said were the ‘bomb targets.’

The team then combined copper sulfide(CuS) and DMXAA, a drug that cuts tumor vascular cells, into the nano platform. The research team told SCMP that when the CuS nanoparticles are exposed to near-infrared light, they generate heat that can destroy cancer cells through a process called photothermal therapy. The DMXAA helps induce the death of tumor vascular cells, ultimately leading to the death of the tumor tissue. This not only kills tumor cells, but the synergy of CuS and DMXAA triggers the body's immune system to fight cancer.

"These platforms have uniform size, good stability, high photothermal conversion efficiency, and satisfactory drug release performance. Cell experiments showed that these platforms have excellent in vitro targeting ability, photothermal ablation ability, and immune activation ability," said Shi Xiangyang, co-author of the paper.

"The nanoplatform has been tested in vitro and shows promising results for breast cancer treatment. We hope that this technology can be further developed for clinical use in the future."

The lead authors of the research - Shi Xiangyang and Cao Xueyan - have been focusing on using nano-biotechnology in cancer treatment for over a decade.

The study was published in a peer-reviewed journal Small, that covers science at the nano and microscale.

Study Abstract:

Development of intelligent nanoplatforms that can simultaneously target multiple factors associated with tumor growth and metastasis remains an extreme challenge. Here, an intelligent dendritic nanodevice incorporating both copper sulfide nanoparticles (CuS NPs) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA, a vascular disrupting agent) within the dendrimer internal cavities and surface modified with a targeting agent LyP-1 peptide is reported. The resulting generation 5 (G5) dendrimer-based nanodevice, known as G5-PEG-LyP-1-CuS-DMXAA NPs (GLCD NPs), possess good colloidal stability, pH-sensitive drug release kinetics, and high photothermal conversion efficiency (59.3%). These functional GLCD NPs exert a LyP-1-targeted killing effect on breast tumors by combining CuS-mediated photothermal therapy (PTT) and DMXAA-induced vascular disruption, while also triggering antitumor immune responses through PTT-induced immunogenic cell death and DMXAA-mediated immune regulation via M1 polarization of tumor-associated macrophages and dendritic cell maturation. In addition, with the LyP-1-mediated proapoptotic activity, the GLCD NPs can specifically kill tumor lymphatic endothelial cells. The simultaneous disruption of tumor blood vessels and lymphatic vessels cuts off the two main pathways of tumor metastasis, which plays a two-pronged role in inhibiting lung metastasis of the breast cancer model. Thus, the developed GLCD NPs represent an advanced intelligent nanoformulation for immune modulation-mediated combination tumor therapy with potential for clinical translations.