Back Cover: Aptamer‐PROTAC Conjugates (APCs) for Tumor‐Specific Targeting in Breast Cancer (Angew. Chem. Int. Ed. 43/2021)

Abstract

…i sa ne merging new technology in drug discovery.I nt heir Research Article on page 23299, Guoqiang Dong, Chunquan Sheng et al. developed the first aptamer-PROTACc onjugate (APC), which showed improved tumor targeting and in vivo protein degradation, leading to enhanced antitumor potencya nd decreased toxicity.

From classic medicinal chemistry to state‐of‐the‐art interdisciplinary medicine: Recent advances in proteolysis‐targeting chimeras technology

“…In view of the high expression of nucleolin in tumor cells 129 and the serum stability of AS1411, 153 they observed the tumor‐targeting characteristics of ZL216 in mice. Combined with the work of He et al., which linked AS1411 to a complete small molecule PROTAC to achieve the targeting function 127 (Figure 10B), it shows that the development of PROTACs with aptamers has a good application prospect.…”

“…He et al. reported the targeting strategy of nucleic acid aptamer‐PROTAC coupling 127 (Figure 7C). They coupled the nucleolin targeting aptamer AS1411 to the hydroxyl group of the VHL ligand of the PROTAC targeting BET via a dithiocarbonate linker.…”

“… Targeting moiety conjugates for targeted delivery. (A) Antibody‐Proteolysis‐targeting chimeras (PROTAC) conjugates are designed to target HER2‐positive cells to induce BRD4 degradation; 123 (B) E3 ligand can be linked to folate, which is able to recognize FOLR1 highly expressed in cancer cells and low in normal tissues; 124 (C) Aptamer AS1411 binds to nucleolin, thus inducing internalization of its coupled PROTAC and is going to be reduced by GSH in tumor cells, releasing active PROTAC 127 …”

“…(a) Aptamer AS1411 was utilized as a warhead and linked to VHL ligand to compose and constituted PROTAC ZL216, which can specifically target nucleolin in tumor cells and degraded nucleolin in vitro and can inhibit the proliferation of breast cancer cells 152 . (b) AS1411 can also be added to a small molecule PROTAC to target the tumor cell 127 …”

Targeted Protein Degradation Technology and Nanomedicine: Powerful Allies against Cancer

“…[ 20,21 ] Another issue is that their catalytic bioactivity and the tendency of sub‐stoichiometric effects indicate that PROTACs may potentially induce unforeseen off‐target effects. Moreover, the design of TPD to a great extent relies on the biomacromolecule components, such as antibodies, [ 12 ] peptides, [ 22 ] and nucleic acid aptamers, [ 23 ] that contributes to potential disadvantages such as short plasma half‐life, immunogenicity, and instability. Meanwhile, nanomedicines have shown great promise to overcome these shortcomings by modulating systemic drug biodistribution and targeted tissue accumulation.…”