Nano-PROTACs: state of the art and perspectives

Abstract

PROteolysis TArgeting Chimeras (PROTACs), as a recently identified technique in the field of new drug development, provides new concepts for disease treatment and is expected to revolutionize drug discovery. With...

Restraining the power of Proteolysis Targeting Chimeras in the cage: A necessary and important refinement for therapeutic safety

“…The inherent instability of PROTACs presents a critical obstacle to their clinical efficacy and safety, manifesting through various deleterious mechanisms (Figure 3). Primarily, this instability can precipitate the premature degradation of PROTACs, thereby significantly diminishing their therapeutic efficacy due to the inability to maintain adequate drug concentrations for efficient protein targeting (Zhong et al, 2024). Furthermore, the degradation products resulting from this instability may possess inherent toxicity, potentially inducing adverse side effects or toxicity in patients (Sun et al, 2019).…”

New implications for prion diseases therapy and prophylaxis

“…Currently, investigations are underway to explore the integration of nanotechnology-based smart delivery systems. These systems aim to synergistically enhance the solubility, permeability, and targeting capability of TPD drugs, thereby reducing the risk of off-target toxicity (Zhong et al, 2024).…”

A photoactivatable upconverting nanodevice boosts the lysosomal escape of PROTAC degraders for enhanced combination therapy

“…25 Moreover, the encapsulation of various drugs within a single nanocarrier allows for their synchronized release at specific sites of action, enhancing the potential for synergistic anti-tumor effects. 26 Therefore, nanocarrier systems are particularly advantageous for delivering PROTACs, 27 as they effectively overcome challenges such as high hydrophobicity and limited cell membrane permeability that are typical of traditional PROTACs. However, these carrier-mediated delivery platforms typically achieve cellular entry via endocytosis and are often entrapped in endo/lysosomes, 28 leading to suboptimal release of PROTACs into the cytosol where they can recruit E3 ubiquitin ligases to degrade target proteins effectively.…”