• Preventing PI3K/AKT/mTOR pathway by nanoparticle loaded inhibitors: a promising approach in cancer therapy
  • zeinab chaharlashkar,1,* Effat Alizadeh,2
    1. 1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. 2. Research Central Lab, Golestan University of Medical Sciences, Gorgan, Iran.
    2. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.


  • Introduction: The PI3K/AKT/mTOR signaling pathway plays a central role in regulating cancer cell survival, proliferation, and metabolism. Aberrant activation of this pathway contributes to tumor progression and therapeutic resistance in various cancers. Although several small-molecule inhibitors, such as MK2206 and Everolimus, have demonstrated promising results in preclinical models, their clinical application remains limited due to poor solubility, non-specific distribution, and systemic toxicity. Nanoparticle-based drug delivery systems offer a talented strategy to overcome these challenges by enhancing drug bioavailability, tumor-specific accumulation, and controlled release. Moreover, functionalization of nanoparticles with ligands such as folic acid, peptides, or antibodies enables active targeting of tumor cells, further improving therapeutic efficiency and reducing side effects. The aim of this work is to provide an overview of recent investigations to block PI3K/AKT/mTOR signaling pathway using nanoparticle loaded inhibitors.
  • Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Google Scholar for original research articles published from 2018 to 2023. Studies were included investigated nanoparticle-mediated delivery of PI3K/AKT/mTOR inhibitors in in vitro or in vivo cancer models.
  • Results: Numerous studies have demonstrated the efficacy of nanoparticle systems in delivering inhibitors to the PI3K/AKT/mTOR pathway. For example, folic acid and berberine-loaded silver (FA-PEG@BBR-AgNPs) nanomaterials successfully inhibiting tumor growth of breast cancer cells, inducing apoptosis with minimal off-target effects. Carboxyl-Functionalized Carbon Nanotubes and cisplatin effectively inhibited PI3K/AKT signaling in triple-negative breast cancer cells. In another study, a disulfied-crosslinked micelle plateform (NanoGe) combination with nanoformulated cabazitaxel (NanoCa) siginificantly improved treatment outcomes, acheieving an 83% cure rate in preclinical prostate cancer models.
  • Conclusion: Functionalized nanoparticles present a promising platform for targeted modulation of the PI3K/AKT/mTOR signaling pathway in cancer therapy. These systems improve drug stability, tumor targeting, and therapeutic efficiency, and hold great potential for future clinical translation in precision oncology.
  • Keywords: Nanoparticles, Drug Delivery, PI3K/AKT/mTOR Pathway, Molecular Inhibitors