Nanoparticles Incorporating a Fluorescence Turn-on Reporter for Real-Time Drug Release Monitoring, a Chemoenhancer and a Stealth Agent: Poseidon’s Trident against Cancer?

• DOI: 10.1021/acs.molpharmaceut.0c00730
• Publication Date: 2020-12-21T17:00:18Z
• Authors: Arjun Attri; Deepak Thakur; Taranpreet Kaur; Sebastian Sensale; Zhangli Peng; Deepak Kumar; Raman Preet Singh
• Keywords: Trident; Turn (biochemistry); Cancer drugs

The rate and extent of drug release under physiological conditions is a key factor influencing the therapeutic activity formulation. Real-time detection by conventional pharmacokinetics approaches confounded low sensitivity, particularly in case tissue-targeted novel delivery systems, where concentrations reach systemic circulation. We present fluorescence turn-on platform for real-time monitoring from nanoparticles based on reversible quenching fluorescein esters. Fluorescein-conjugated carbon nanotubes (CNTs) were esterified with methotrexate solution solid phase, followed supramolecular functionalization chemoenhancer (suramin) or/and stealth agent (dextran sulfate). Suramin was found to increase cytotoxicity A549 cells. On other hand, dextran sulfate exhibited no effect or cellular uptake CNTs cells, while decrease observed macrophages (RAW 264.7 cells). Similar results also obtained when replaced graphene. Docking studies revealed that conjugates are not internalized folate receptors/transporters. Further, docking molecular dynamics do exhibit affinity toward target, dihydrofolate reductase. Molecular distinct features dextran-CNT suramin-CNT interactions, characterized π-π interactions between dextran/suramin. Our study provides simple, cost-effective, scalable method synthesis conferred ability monitor real-time. This could be extended drugs types nanoparticles.