A BRD4 PROTAC nanodrug for glioma therapy via the intervention of tumor cells proliferation, apoptosis and M2 macrophages polarization

Targeted nanomedicines remodeling immunosuppressive tumor microenvironment for enhanced cancer immunotherapy

“…For example, Yang et al. 161 constructed a BRD4 decorated amphiphilic micelle carrying ARV-825 for glioma treatment, which suppressed M2-like TAMs polarization through the inhibition of interferon regulatory factor 4 (IRF4) promoter transcription and phosphorylation of STAT3, STAT6 and protein kinase B. Other inhibiting agents, such as zoledronic acid and hispanolone derivative 8,9-dehydrohispanolone-15,16-lactol, were proved effective as well 162 , 163 .…”

PROTACs in Epigenetic Cancer Therapy: Current Status and Future Opportunities

“…The fusion of ARV-825 and nanotechnology has enabled the targeting of multiple cancers to achieve better therapeutic effects and also provides a new treatment method for drug-resistant cells [ 43 , 44 ]. The massive infiltration of tumor-associated macrophages in gliomas hinders the efficacy of drugs; however, incorporating ARV-825 into PEG composed of substance P peptides therapeutic nanosystems constructed in composite micelles enables penetration of the blood–brain barrier to target brain tumors, attenuate cell proliferation, induce apoptosis, and inhibit M2 macrophage polarization, with consequent anti-tumor effects [ 45 ]. In antiretroviral drug-loaded PEG-polylactic-co-glycolic acid polymer nanoparticles in pancreatic cancer two-dimensional cell culture and three-dimensional multicellular tumor spheroids, the model can continue to explain that BRD4 shows a good anticancer effect and can effectively treat pancreatic cancer [ 46 ].…”

Critical involvement of lysyl oxidase in seizure-induced neuronal damage through ERK-Alox5-dependent ferroptosis and its therapeutic implications

“…Furthermore, to assess the clinical translation potential of BAPN-based therapy, we systematically evaluated the safety of BAPN and found that it has evident toxic effects, especially against the heart and nerve system. To minimize the side effects of BAPN, we adopted the brain targeting drug delivery nanotechnology, which is a promising therapeutic approach against neurological diseases such as epilepsy 28 , glioma 29 and brain metastasis 30 . Our results illustrated that BAPN-associated cardiotoxicity and neurotoxicity were efficiently abrogated through encapsulation with bioresponsive amorphous calcium carbonate-based nanocarriers.…”