New nanoparticle proposed as treatment for a ‘wide range of cancers’
Materials scientists working in the oncology space find biocompatible polymeric and lipid nanoparticles of interest because they are relatively easily modified as a means of targeting their respective disease environments, but the tumor microenvironment varies considerably from one cancer to the next. Molecular heterogeneity is also a challenge, and consequently, current nanomedicine approaches rely extensively on passive drug targeting mechanisms that exploit leaky tumor vasculature. Researchers at Kansas State University sought to address these issues and the need for both immunocompatibility and aqueous stability by developing a receptor-specific composite of polymers and lipids, singling out the LyP-1 peptide. LyP-1 is integrated in a core-shell polymer-lipid composite nanoparticle that is designed to target overexpression of the mitochondrial p32 protein. This particle is described as using poly(lactide-co-glycolic acid) as a skeleton and a cargo reservoir, and a phospholipid with polyethylene glycol as a stabilizer. The researchers studied this combination’s cellular interaction and targeting ability by “accessing the full spectrum of biodistribution” with the help of labeling with near-infrared dye to provide in vivo imaging. The nanoparticles are more or less spherical and average roughly 68 nanometers, and are said to be highly stable in physiological conditions with a low polydispersity index. In vitro testing demonstrated “excellent biocompatibility” as well as significantly higher uptake by mouse osteosarcoma compared to non-cancerous fibroblasts. Similarly, these LyP-1 nanoparticles demonstrated a tripling of tumor accumulation compared to the non-targeted counterparts in the animal tumor. “Considering the overexpression of p32 in many cancers, the proposed nanoconstruct could hold promises in the therapeutic planning of a wide range of tumors,” the authors concluded. This work is explained in more detail in the May 11, 2020, online issue of Materials Advances.
CD163-expressing macrophages a sign of poor outcomes
The conversion of circulating monocytes into macrophages is not an exhaustively explained process, and researchers in France and Brazil have some good news in that they have shed some light on some of the underlying processes. There seems to be an association between poor outcomes in breast cancer and tumor-associated macrophages (TAMs) that express high levels of the CD163 protein, however, a finding that may give clinicians and patients a leg up in efforts to beat breast cancer. The researchers used multicolor flow cytometry to evaluate TAM phenotypes in more than 90 breast cancer patients, and cultured monocytes from healthy donors were exposed to fluids (supernatant) drawn from sliced primary tumors in an effort to gain some insight into the monocyte-to-macrophage conversion process. The results suggest that a high density of intra-tumor TAMs that express CD163 is predictive of reduced survival in breast cancer patients, while vascular endothelial growth factor, among others, seen in the tumor supernatant served to fuel a conversion of monocytes to cytokines that suppress CD4+ T cells. Interestingly, blood monocytes from roughly 40% of these patients exhibited an “altered response to in vitro stimulation,” such as a higher rate of secretion of immunosuppressive and angiogenic cytokines that are commonly associated with metastasis. The authors said their results suggest a novel mechanism of tumor escape in breast cancer, which may include a systemic trigger for metabolic impairment that in turn creates a functional bias that favors tumor growth. These results are described in greater detail in Clinical and Translational Immunology.
Mevion inks deal for protons in Texas
Mevion Medical Systems Inc., of Littleton, Mass., said it has agreed to build one of its S250i proton beam therapy systems for an unnamed independent service provider located in Texas. Mevion said the unit will feature the company’s Hyperscan pencil-beam scanning technology and that the contract will be completed at some point in the second half of 2020. This will be the first compact proton beam therapy system in Texas, the company said.
PSMA PET-CT show well in study of prostate cancer metastasis
Accurately depicting the spread of a cancer is critical to improving outcomes, and a recent study of prostate-specific membrane antigen (PSMA) PET-CT imaging suggests this modality gives the patient and clinician a clear understanding of prostate cancer metastasis. The U.S. National Cancer Institute said in a May 11 statement that an Australian trial demonstrated that this modality handily beat the combined power of a CT scan and a bone scan to detect metastatic tumors, but was also more likely to prompt a change in treatment planning as well. While this study was not designed to evaluate outcomes such as survival, but the results corroborate those seen in similar studies conducted in Europe. At this point, the FDA has not approved a PSMA agent, but that could change, given that this imaging process not only was more accurate for detecting metastases, but also cut down on the exposure to radiation seen in conventional efforts to evaluate prostate cancer metastasis.