Jain explains that the pacemaker therapy seems to help normalize the tumor microenvironment – meaning it helps correct some of the abnormalities that develop around the tumor to protect the tumor and promote growth. and its spread. For example, while tumors can send out signals that compromise normal blood flow and suppress immune cell responses (both of which make them difficult to treat), metronotherapy seems to such as improved vascular function and immune activation in tumors. Recent preclinical studies suggest that nanotherapy can induce similar changes in the tumor microenvironment.
“In this study, we hypothesized that nanoparticle formulations, with their mass-controlled release and long circulation time, could trigger a chain of action like this,” says Jain. pacemaker therapy”.
Using a mathematical framework and experiments conducted in mice, the team showed that both approaches can be considered “normalizing strategies” to influence the tumor microenvironment and improve the quality of life. improve cancer treatments. Additionally, in mice with triple-negative breast cancer or fibroids, Doxil — a nanodrug approved for the treatment of metastatic breast cancer and consisting of doxorubicin enclosed in a lipid sphere — was administered. Administered via a heart rate monitoring schedule can overcome the tumor resistance commonly seen with Doxil. a standard dosing schedule. A pacing schedule also improves the effectiveness of combining Doxil with a type of immunotherapy called an immune checkpoint inhibitor.
“Nanoimmunotherapy, which combines nanoimmunotherapy with immunotherapy, has great potential to improve patient outcomes and for this reason, understanding resistance mechanisms and developing Strategies to enhance nanoimmunotherapy in breast and other cancers are needed.” says co-author Triantafyllos Stylianopoulos, PhD, Director of the Cancer Physiology Laboratory and an associate professor at the University of Cyprus. “The results of this study could be the basis for planning future clinical studies to improve the effectiveness of nanoimmunotherapy regimens.”
The results suggest that combining nanotherapies with heart rate-controlled scheduling can lead to a powerful attack against hard-to-treat tumours. By working together to normalize the tumor microenvironment, these two strategies give the drug a better chance of reaching cancer cells and effectively targeting them.
Study co-authors include Fotios Mpekris and Myrofora Panagi (University of Cyprus), Chrysovalantis Voutouri (Massachusetts General Hospital) and James W. Baish (Bucknell University).
This work was supported by grants from the National Foundation for Cancer Research, the Ludwig Center at Harvard; Jane’s Trust Fund; Nile Albright Medical Research Foundation; US National Cancer Institute grade R35-CA197743, R01-CA208205, R01-CA259253, R01NS118929, U01CA224348, U01CA261842 (for RKJ); European Research Council (ERC-2013-StG-336839, ERC-2019-CoG-863955); and Cyprus Research and Innovation Fund (INFRASTRUCTURE / 1216/0052, POST-DOC / 0718/0084) (to TS), Marie Sk³odowska Curie Actions Individual Fellowship Global Fellowship (MSCA-IF-GF-2020-101028945) (to CV) and Grant R01 HL128168 (to JWB).