Dendronized DNA Chimeras Harness Scavenger Receptors To Degrade Cell Membrane Proteins

Abstract

Bispecific chimeras bridging cell membrane proteins with lysosome‐trafficking receptors (LTRs) provide an effective therapeutic approach through lysosomal degradation of disease‐relevant targets. Here, we report a novel dendronized DNA chimera (DENTAC) strategy that uses a dendritic DNA to engage cell surface scavenger receptors (SRs) as LTR. Using bioorthogonal strain‐promoted alkyne‐azide cycloaddition to conjugate the dendritic DNA with protein binder, the resulting DENTAC is able to traffic the protein target into the lysosome for elimination. We demonstrated the utility of DENTAC by degrading oncogenic membrane nucleolin (NCL) and epidermal growth factor receptor (EGFR). The anti‐cancer application of NCL‐targeting DENTAC was validated in a mouse xenograft model of lung cancer. This work thus presents a new avenue for rapid development of potent degraders against membrane proteins, with also broad research and therapeutic prospects.

pH-Activatable Charge-Reversal Polymer-Based Nanocarriers for Targeted Delivery of Antihepatoma Compound

“…The red fluorescence was visualized after the incubation of tumor cells with RhB@MI 7 -β-CD/SA NPs for 2 h and co-localized with the green fluorescence of endosomes/lysosomes (shown as yellow fluorescence). The reasons may be attributed to the fact that SR on the surface of tumor cells acts as an anion ligand-binding receptor, while the polyanionic nanomaterials can target SR and then induce drug internalization into lysosomes via caveolae-mediated endocytosis . The results demonstrated that RhB@MI 7 -β-CD/SA NPs were initially internalized by tumor cells, then transported to endosomes/lysosomes for intracellular trafficking, ultimately leading to the cargo release and effective accumulation inside tumor cells. , …”

Bi nanoparticles confined in N,S co-doped carbon nanoribbons with excellent rate performance for sodium-ion batteries

“…The rate capability result demonstrates that the N,S-C@Bi/CNT anode has superior rating performance in high current density when compared with previously reported Bi anode materials. 37,43–48 In addition, the galvanostatic charge–discharge platform profiles of these two samples at different current densities were tested, as shown in Fig. S7 †.…”

An update on chiral phosphoric acid organocatalyzed stereoselective reactions

“…In this context, Zhu et al have reported a Diels–Alder reaction of 2-trifluoroacetamido-1,3-dienes and α,β-unsaturated carbonyl compounds to afford 1-trifluoroacetamido cyclohex-1-ene derivatives 27 (Scheme 26). 96 The exploration of diverse dienophiles in the CPA-catalyzed cycloaddition reaction produced moderate to excellent yields with good to excellent enantioselectivities (52–96% yields, 83–99% ee). Then, 4-aryl or 4-alkyl substituted dienes were evaluated.…”