News

Calcium bursts kill drug-resistant tumor cells

Calcium bursts kill drug-resistant tumor cells
Technology
Multidrug resistance (MDR) -- a process in which tumors become resistant to multiple medicines -- is the main cause of failure of cancer chemotherapy. Tumor cells often acquire MDR by boosting their production of proteins that pump drugs out of the cell, rendering the chemotherapies ineffective. Now, researchers reporting in ACS Nano Letters have developed nanoparticles that release bursts of calcium inside tumor cells, inhibiting drug pumps and reversing MDR.

advertisement

A pump protein called P-glycoprotein (P-gp) often plays a key role in MDR. P-gp is in the cell membrane, where it uses energy in the form of adenosine triphosphate (ATP) to pump drugs out of tumor cells. Scientists have tried to block P-gp in various ways, such as with small-molecule inhibitors or by depleting ATP. However, the strategies used so far can cause side effects, or they are unstable in the body. Some of the treatments can be difficult to prepare. Kaixiang Zhang, Zhenzhong Zhang, Jinjin Shi and colleagues wanted to block P-gp using a different approach. Previous research suggested that overloading tumor cells with calcium ions could both decrease production of P-gp and reduce ATP levels. But the team needed to find a way to deliver bursts of calcium, along with a chemotherapy drug, inside cancer cells.

The researchers made a "calcium ion nanogenerator" (TCaNG) by loading calcium phosphate nanoparticles with the chemotherapy drug doxorubicin and then coating them with molecules that would allow TCaNG to target and enter cancer cells. Once inside cells, TCaNGs entered an acidic compartment, where the TCaNGs disintegrated, releasing both doxorubicin and bursts of calcium ions. When the team tested TCaNG on cancer cells in a petri dish in the lab, both ATP and P-gp production decreased, which allowed doxorubicin to kill the previously resistant tumor cells. When tested in tumor-bearing mice, TCaNG-treated mice showed significantly smaller tumors after 21 days of treatment than control mice, with no apparent side effects.

Materials provided by American Chemical Society . Note: Content may be edited for style and length.

American Chemical Society. "Calcium bursts kill drug-resistant tumor cells." ScienceDaily. ScienceDaily, 16 October 2020. .

American Chemical Society. "Calcium bursts kill drug-resistant tumor cells." ScienceDaily. www.sciencedaily.com/releases/2020/10/201016132017.htm (accessed October 17, 2020).

advertisement

1

Aug. 21, 2018 — The results of a large, international systematic review show that tuberculosis treatment is successful in children with multidrug-resistant tuberculosis (MDR-TB). The study was used to inform the ...

June 20, 2017 — Antibiotics were the wonder drug of the 20th century, but bacteria evolved resistance. According to the CDC, more than 2 million people in the U.S. develop MDR infections every year. Researchers have ...

Mar. 23, 2017 — The rise of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) threatens to derail decades of progress in controlling the disease, according to a new ...

Aug. 24, 2016 — Multidrug resistance (MDR) is the mechanism by which many cancers develop resistance to chemotherapy. Researchers have developed nanoparticles that simultaneously deliver chemotherapy drugs to tumors ...
Read more on sciencedaily.com
News Topics :
RELATED STORIES :
Technology
UConn associate professor of pharmaceutics Xiuling Lu, along with professor of chemistry Rajeswari M. Kasi, was part of a team that recently published a paper in Nature Cell Biology finding...
Technology
Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy. If scientists could put a homing beacon in tumors, they could attract these medicines and...
Science
Sooner or later, most cancer patients develop resistance to the very chemotherapy drugs designed to kill their cancer, forcing oncologists to seek alternatives. Even more problematic, once a patient s...
Technology
Researchers at the University of Illinois at Chicago have demonstrated that magnetic nanoparticles can be used to ferry chemotherapy drugs into the spinal cord to treat hard to reach spinal tumors in...
Science
Delivering chemotherapy drugs in nanoparticle form could help reduce side effects by targeting the drugs directly to the tumors. In recent years, scientists have developed nanoparticles that deliver one or...