Oral anticancer drug bound to nanoparticles for nasal delivery

Low dosage could minimize immunosuppressive side effects

From left: Yang Seung-ho, professor of neurosurgery at Seoul St. Mary's Hospital; Park Sung-min, professor of IT convergence engineering at POSTECH; and Kim Won-jong, professor of chemistry at POSTECH. [Seoul St. Mary's Hospital]
From left: Yang Seung-ho, professor of neurosurgery at Seoul St. Mary's Hospital; Park Sung-min, professor of IT convergence engineering at POSTECH; and Kim Won-jong, professor of chemistry at POSTECH. [Seoul St. Mary's Hospital]

South Korean researchers have confirmed a technique that bypasses the blood-brain barrier — the biggest obstacle in treating glioblastoma, one of the most intractable brain tumors — to deliver anticancer drugs precisely to the tumor site.

A joint research team led by Yang Seung-ho, a neurosurgery professor at the Catholic University of Korea's Seoul St. Mary's Hospital, Park Sung-min, a professor of IT convergence engineering at POSTECH, and Kim Won-jong, a professor of chemistry at POSTECH, announced Thursday that they had developed a new drug delivery method. The method administers anticancer nanoparticles through the nose, then uses a magnetic field to guide them to a malignant brain tumor. Tests on animal models confirmed a significant extension in survival.

Glioblastoma is the most common type of primary malignant brain tumor in adults, accounting for roughly 65 percent of all primary malignant central nervous system tumors. Data from the National Cancer Information Center show a 10-year survival rate of just 5.3 percent, reflecting an extremely poor prognosis.

The key innovation in this research was not the development of a new drug, but a change in the route by which an existing drug reaches the tumor.

Temozolomide, the standard oral drug currently used to treat glioblastoma, has low therapeutic efficacy after administration and causes systemic side effects including immunosuppression. The primary reason is that the blood-brain barrier, which biologically protects the brain, blocks the drug from penetrating to the tumor.

The research team combined two ideas: the olfactory nerve, which connects directly to the brain, provides a natural pathway from the nose into brain tissue; and magnetically charged nanoparticles can have their direction of movement controlled by an external magnetic field.

The team synthesized a compound — TMZ-SPION — by binding temozolomide (TMZ) to superparamagnetic iron oxide nanoparticles (SPION) roughly 56 nanometers in size. The compound was administered through the nose, then guided to the tumor site using transcranial magnetic stimulation (TMS).

In cell experiments, the TMZ-SPION compound showed tumor cell-killing efficacy equivalent to that of the conventional drug. Electron microscopy analysis confirmed that the nanoparticles were distributed evenly inside the nuclei of tumor cells.

In animal experiments, the compound was administered to glioblastoma model mice and survival was tracked over 90 days. Median survival was 27 days in the control group, 51 days in the group that received the compound alone, and 72 days in the group that received the compound followed by transcranial magnetic stimulation.

Compared with the untreated control group, the combination group — compound plus TMS — showed a survival extension of approximately 2.7 times, while the compound-only group showed an extension of approximately 1.9 times.

Particularly notable was the dosage. The drug dose administered to the combination group was only about 5.6 percent — roughly one-eighteenth — of the standard oral dose, yet still produced a significant extension in survival.

Yang, who also serves as director of the Gamma Knife Center at Seoul St. Mary's Hospital and president of the Korean Society for Nanomedicine, said the approach "is considered clinically significant in that it can effectively bypass the blood-brain barrier while substantially reducing existing side effects such as systemic immunosuppression." He added that he hopes the method "can contribute to transforming glioblastoma into a disease that can be managed over the long term."

The research was published in the international journal Drug Delivery and Translational Research.


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