We developed supramolecular self-assembled nanoparticles for targeting the endoplasmic reticulum (ER) in cancer cells.

The endoplasmic reticulum (ER) primarily guides protein synthesis, folding, transport, and lipid biosynthesis inside the cells. As a result, dysregulation in those cellular functions leading to ER stress has recently emerged as one of the hallmarks of cancer. Yet, precise navigation in the ER in cancer cells has continued to be a formidable task. Herein, we engineered a lipid nanoparticle (17AAG-ER-NP) containing (a) ER targeting moiety (Tosyl), (b) fluorescent tag with DNA damaging capability (1,8-naphthalimide), and (c) ER stress inducer (17AAG, Hsp90 inhibitor). These lipidic nanoparticles were confined in the ER of HeLa cells over 6 h through caveolin-controlled endocytosis confirmed by confocal microscopy. Western blot analysis, fluorescent microscopy, and flow cytometry studies confirmed that 17AAG-ER-NPs can concurrently activate ER stress and nuclear DNA impairment for arresting the cell cycle in the G2-M phase to elicit late apoptosis, followed by cell death, in a greatly augmented manner compared to free drugs. Interestingly, this nanoparticle-mediated ER stress activated autophagy, which was suppressed through a cocktail treatment with 17AAG-ER-NPs and chloroquine (autophagy inhibitor), prompted remarkable HeLa cell killing at submicromolar concentration. This nanoplatform can support new tools to impair multiple targets in the ER for future cancer therapy.

Polymer modified self-assembled graphene oxide nanoparticles are developed for targeting cancer cells.

We have engineered graphene oxide based nanocell to target DNA topoisomerases and nuclear DNA in cancer cells to induce apoptosis.

Chalcone and boronic acids are important privileged structures in myriads of natural and synthetic products having diverse biological activities. However, their therapeutic window is highly narrow due to their hydrophobic nature affecting unpredictable biodistribution. To address this, we herein have synthesized a novel hybrid glycosylated chalcone−boronic acid library. Cell viability, flow cytometry, confocal microscopy, and gel electrophoresis assays demonstrated that one of the library members induces cell cycle arrest in the G2/M phase through the activation of p21 and decrease levels of cyclin B1 and CDK1. In addition, it also induces apoptosis, primarily due to the inhibition of Bcl-2/ Bcl-xl and the augmentation of BAX to prompt mitochondrial damage and reactive oxygen species generation. Most interestingly, the lead cytotoxic glycosylated chalcone−boronic acid selfassembled in water into a spherical nanodrug that can further entrap another anticancer drug (doxorubicin) to show remarkably improved efficacy in breast cancer cells. This novel lead compound has prospective as a vector-free nanodrug for combination cancer therapy.