New nanomedicine targeting hydroxyapatite could be a paradigm shift for cancer treatment

A multidisciplinary research team from Vanderbilt University and Vanderbilt University Medical Center has discovered a new way to kill a tumor by disrupting its acidic “microenvironment” without harming normal tissue.

The target of this unorthodox approach is hydroxyapatite (HAP), a natural mineral that is a major component of bones and teeth, but is also produced by some tumors.

In the extracellular microenvironment that surrounds and nourishes tumors, PAH crystals can enhance tumor cell proliferation, progression, and migration (metastasis). However, PAH is absent in normal soft tissues, making it an attractive target for cancer imaging and treatment.

Using various molecular analysis methods, researchers identified and synthesized a nanoparticle that, when administered via an injectable solution called NSPS, chelates or binds to calcium on tumor-associated PAH crystals, thus causing it to dissolve.

Dissolution triggered localized alkalosis, a sudden reversal in the acidity of the tumor microenvironment strong enough to kill breast cancer cells grown in culture and to slow tumor growth in animal models of human breast, colon, and cervical cancers. lung and prostate.

At the same time, NSPS demonstrated limited interaction with normal soft tissue and bone, the researchers report in the journal Cancer Medicine. These results suggest that NSPS could be, in their words, “one-of-a-kind and first in a class of new cancer treatments.”

The article’s corresponding author, Mohammed Tantawy, Ph.D., MBA, is a research associate professor of radiology and radiologic sciences and a member of the Vanderbilt University Institute for Imaging Sciences at VUMC.

The microenvironment of tumors is generally more acidic than that of surrounding normal tissues. Acidity, by altering the structure or absorption of anticancer drugs, may contribute to the chemotherapy resistance exhibited by tumors such as triple negative breast cancer, which has a high recurrence rate and poor overall survival.

“There is an urgent clinical need for new treatment paradigms that may improve outcomes for cancer patients with a poor prognosis,” the researchers noted. Although further studies in humans are needed, “NSPS has significant potential to be a breakthrough approach for the treatment of cancer patients with a poor prognosis.”

Tantawy added: “At the Institute of Imaging Sciences, we are fortunate to be able to lead projects like this from initial design through the development of novel ligands for cancer detection and treatment. to in vivo demonstrations based on multimodal imaging and even in human subjects. “.