The impact of nanomaterials on autophagy across health and disease conditions

Abstract

Autophagy, a catabolic process integral to cellular homeostasis, is constitutively active under physiological and stress conditions. The role of autophagy as a cellular defense response becomes particularly evident upon exposure to nanomaterials (NMs), especially environmental nanoparticles (NPs) and nanoplastics (nPs). This has positioned autophagy modulation at the forefront of nanotechnology-based therapeutic interventions. While NMs can exploit autophagy to enhance therapeutic outcomes, they can also trigger it as a pro-survival response against NP-induced toxicity. Conversely, a heightened autophagy response may also lead to regulated cell death (RCD), in particular autophagic cell death, upon NP exposure. Thus, the relationship between NMs and autophagy exhibits a dual nature with therapeutic and environmental interventions. Recognizing and decoding these intricate patterns are essential for pioneering next-generation autophagy-regulating NMs. This review delves into the present-day therapeutic potential of autophagy-modulating NMs, shedding light on their status in clinical trials, intervention of autophagy in the therapeutic applications of NMs, discusses the potency of autophagy for application as early indicator of NM toxicity.

Keywords: Autophagic flux; Autophagy blockade; Environmental toxicity; Nanoparticles; Nanoplastics; Regulated cell death.

Fig. 1

Autophagy and nutrient availability. Nutrients availability differentially regulates mTOR and AMPK signaling pathways which interact in a complex interplay

Fig. 2

Schematic representation of potential modulatory effects of NMs on autophagy pathway

Fig. 3

Approved trials with NMs as drug carriers. NMs carrying anticancer drugs based on autophagy modulation have been employed for the treatment of cancer. Here, examples of approved trials involving bioactive molecules at different clinical phases are reported. This figure was created using Biorender.com

Fig. 4

NMs differentially regulate autophagy. Schematic representation of autophagy being a pro-death and pro-survival mechanism in response to nanomaterial exposure is showed here. Autophagy is also activated as a supporting mechanism for cell death