Enzyme-responsive micellar JQ1 induces enhanced BET protein inhibition and immunotherapy of malignant tumors

Abstract

The bromodomain and extra-terminal (BET) proteins are attractive targets for treating various malignancies including melanoma. The inhibition of BET bromodomains e.g. with JQ1 is found to downregulate the expression of...

A polymeric IDO inhibitor based on poly(ethylene glycol)-b-poly(l-tyrosine-co-1-methyl-d-tryptophan) enables facile trident cancer immunotherapy

“…The significantly decreased PD-L1 expression induced by cRGD-NPDJ could be attributed to JQ1 suppressing the transcription of oncogene c-MYC, and thus downregulating the PD-L1 protein on the surface of cancer cells. 35,36…”

“…The significantly decreased PD-L1 expression induced by cRGD-NPDJ could be attributed to JQ1 suppressing the transcription of oncogene c-MYC, and thus downregulating the PD-L1 protein on the surface of cancer cells. 35,36 3.5 In vivo antitumor efficacy DOX-loaded nanoparticles without 1-MT (NPD w/o 1-MT) formed from PEG-PTyr were utilized as a control to explore the possible efficacy of the developed polymeric IDO inhibitor. At a DOX dose of 5 mg kg −1 , NPD revealed an obviously better tumor inhibition effect than NPD w/o the 1-MT group, in which two thirds of the mice in the NPD group exhibited retarded tumor growth during the experimental period (Fig.…”

Stimuli‐Responsive Nanoradiosensitizers for Enhanced Cancer Radiotherapy

“…[147,148] Therefore, both MMPs and cathepsin-B have been explored to develop enzyme-responsive nanoplatforms aimed at significantly enhancing RT efficacy and minimizing damage to surrounding normal tissues. [149,150] Wang et al prepared a multifunctional enzyme-responsive peptide modified ultrasmall Au NPs (Au@Tat-R-EK) to achieve enhanced RT by targeting tumor cells (Figure 6A). [151] The peptide consisted of three different ingredients: the first section was a Tat protein peptide sequence (GRKKRRQRRRPQ) derived from HIV-1 transactivator of transcription; the second segment was a cathepsin B peptide (GFLG), which served as a cleavable linker specifically cleaved by overexpressed cathepsin B in various malignant tumors; and the outer layer was a zwitterionic antifouling peptide (EKEKEKEKEK) that covered Au NPs and enabled superior blood circulation and passive accumulation in the tumor nucleus.…”

“…[ 147,148 ] Therefore, both MMPs and cathepsin‐B have been explored to develop enzyme‐responsive nanoplatforms aimed at significantly enhancing RT efficacy and minimizing damage to surrounding normal tissues. [ 149,150 ]…”

Development of nanotechnology-mediated precision radiotherapy for anti-metastasis and radioprotection

“…[221][222][223][224][225] The radiosensitizers in response to diverse types of enzymes have been reported to specifically enhance RT and reduce adverse effects on healthy tissues for precision RT. [226][227][228] For example, Ding et al designed multifunctional responsive peptide-modified AuNPs (Au@Tat-R-EK) for tumor-specific targeted RT (Fig. 11a).…”