Self-driven electrical triggering system enhances drug delivery in bladder cancer therapy

One of the major challenges in bladder cancer treatment has always been poor drug penetration into tumor tissue. But a new technology that creates nanotube pathways among bladder cancer cells can improve delivery of chemotherapeutic drugs and strengthen tumor-killing effectiveness, according to a new study in animals published in the November issue of Nature Communications.

Hydroxycamptothecin has demonstrated in lab studies to have an anticancer effect but has poor stability and solubility. Derivatives of hydroxycamptothecin, such as Hycamtin (topotecan) and Camptosar (irinotecan), have been developed by pharmaceutical companies to treat various cancers, including non-small cell lung cancer and colon cancer.

Now researchers from China, Taiwan and London have developed a new way to deliver hydroxycamptothecin by generating electrical fields that create “nanotube highways” for a more uniform drug penetration. The technology uses barium titanate, a ceramic material that has electrical properties and is used in electronics, lenses and prisms.

Researchers noted that the technology they created works to form tunneling nanotubes, which are long, thin cellular structures that connect cells to one another. By activating the formation of these structures, the researchers were able to create efficient conduits through which anti-cancer drugs could move rapidly and in concentrated form into tumor cells.

“These nanotubes act as microscopic passageways that allow material to travel directly from one cell to another,” the authors wrote.

Researchers, led by Zhijun Liu, Ph.D., with the Department of Haematology at the Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital in Chengdu, China, tested this technology in mice and rabbit bladder cancer cell lines. They conducted experiments introducing hydroxycamptothecin and folic acid, which is used as a targeting agent, after activating nanotube formation.

The treated cancer cells showed significantly greater uptake of the drug and a substantial reduction in proliferation compared with cells exposed to drug therapy without nanotube activation.

The study also tested the treatment in the animals and reported that activated cells migrated more slowly and formed far fewer colonies in growth assays, suggesting a direct impact on tumor aggressiveness.

When hydroxycamptothecin was delivered directly into the bladder following nanotube activation, tumors exhibited significantly reduced growth and improved treatment response. The researchers observed limited harm to surrounding normal cells, indicating a degree of selectivity that could be particularly valuable in bladder cancer where preserving healthy tissue is important for function and quality of life.

Liu noted the work may represent a new therapeutic approach in oncology by making use of intercellular communication networks rather than trying to circumvent them. He added that tunneling nanotubes have been observed in a wide range of cancer types, raising the possibility that the technology could extend to solid tumors beyond bladder cancer. Because many cancers share the problem of poor drug penetration, nanotube-based delivery could address a common barrier across multiple diseases.

The researchers warned that the technology remains in an early stage and is not ready for clinical use. Future research, they said, will examine long-term safety, optimal delivery timing and dosage, and whether the effects translate to larger and more diverse animal models before the therapy can advance to human trials. They also plan to investigate the interaction between nanotubes and various classes of chemotherapy to determine whether the approach could enhance effectiveness across different drug categories.

And even though more study is needed, the findings offer promise for a therapeutic strategy that uses a tumor’s own biology to overcome long-standing treatment barriers.