Minibeam radiation therapy enhanced tumor delivery of PEGylated liposomal doxorubicin in a triple-negative breast cancer mouse model

Abstract

Background: Minibeam radiation therapy is an experimental radiation therapy utilizing an array of parallel submillimeter planar X-ray beams. In preclinical studies, minibeam radiation therapy has been shown to eradicate tumors and cause significantly less damage to normal tissue compared to equivalent radiation doses delivered by conventional broadbeam radiation therapy, where radiation dose is uniformly distributed. Methods: Expanding on prior studies that suggested minibeam radiation therapy increased perfusion in tumors, we compared a single fraction of minibeam radiation therapy (peak dose:valley dose of 28 Gy:2.1 Gy and 100 Gy:7.5 Gy) and broadbeam radiation therapy (7 Gy) in their ability to enhance tumor delivery of PEGylated liposomal doxorubicin and alter the tumor microenvironment in a murine tumor model. Plasma and tumor pharmacokinetic studies of PEGylated liposomal doxorubicin and tumor microenvironment profiling were performed in a genetically engineered mouse model of claudin-low triple-negative breast cancer (T11). Results: Minibeam radiation therapy (28 Gy) and broadbeam radiation therapy (7 Gy) increased PEGylated liposomal doxorubicin tumor delivery by 7.1-fold and 2.7-fold, respectively, compared to PEGylated liposomal doxorubicin alone, without altering the plasma disposition. The enhanced tumor delivery of PEGylated liposomal doxorubicin by minibeam radiation therapy is consistent after repeated dosing, is associated with changes in tumor macrophages but not collagen or angiogenesis, and nontoxic to local tissues. Our study indicated that the minibeam radiation therapy’s ability to enhance the drug delivery decreases from 28 to 100 Gy peak dose. Discussion: Our studies suggest that low-dose minibeam radiation therapy is a safe and effective method to significantly enhance the tumor delivery of nanoparticle agents.

Bibliometric and visualization analysis of radiation brain injury from 2003 to 2023

“…The way malignancies are treated in industrialized nations like the US might be connected to this trend. Radiotherapy is the main treatment for 50% of patients in North America with brain tumors ( 38 ). RBI are becoming more commonplace as a result of improved radiation therapy techniques and longer survival times.…”

Nanoradiosensitizer with good tissue penetration and enhances oral cancer radiotherapeutic effect

“…Mini-beam radiation as the third-generation synchrotron apparatus has a smaller beam size, effectively improving the useful diffraction and the focus beam with the high damage ratio could reduce the side effect of normal tissues. Combined with mini-beam radiation, William Zamboni's recent work produced a 7.1-fold greater increase in the tumor delivery of NPs in triple-negative breast cancer xenograft model, which could further enhance the synergistic effect of chemoradiotherapy [49].…”

Combining Nanocarrier-Assisted Delivery of Molecules and Radiotherapy

“…In order to overcome this problem, efforts are put into using nonsynchrotron irradiators (such as a conventional X-ray tube) to produce microbeams [125]. Another strategy consists of using slightly wider 'minibeams' (beam widths ~500-700 µm), which are more easily produced with custom multislit collimators placed in small animal irradiators, as compared to microbeams [124,126,127]. Minibeam radiation therapy (MBRT) leads to similar radiobiological effects as compared to MRT and is also hypothesized to improve the delivery of nanocarriers.…”

“…Animals were irradiated with either MBRT (28 Gy) or broadbeam radiation therapy (7 Gy) and 24 h later received the liposomal DXR. The delivery of liposomal DXR to the tumor was increased by 7.1-fold for MBRT and 2.7-fold for broadbeam radiation therapy compared to liposomal DXR alone (sham RT) [127].…”