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Nano Letters

Multidrug resistance (MDR) 鈥撯€� a process in which tumors become resistant to multiple medicines 鈥撯€撎齣s 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鈥� Nano Letters have developed nanoparticles that release bursts of calcium inside tumor cells, inhibiting drug pumps and reversing MDR.

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 鈥渃alcium ion nanogenerator鈥� (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.

The authors acknowledge funding from the, the Innovation Talent Support Program of Henan Province, Key Scientific Research Projects and the Postdoctoral Science Foundation of China.

The American Chemical 中国365bet中文官网 (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS鈥� mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and its people. The 中国365bet中文官网 is a global leader in providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, eBooks and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a specialist in scientific information solutions (including SciFinder^庐 and STN^庐), its CAS division powers global research, discovery and innovation. ACS鈥� main offices are in Washington, D.C., and Columbus, Ohio.