EndoTAG-1

Cancer is the second-leading cause of death in the 21st century, where early detection and appropriate therapeutic interventions are two components essential for effective cancer management. Despite the availability of several conventional diagnostics and therapeutic agents, cancer mortality rates are rising due to an increase in the frequency of recurrence and metastasis in cancer patients. Therefore, tremendous efforts have been expended to address this significant clinical issue and improve therapeutic efficacy. In this regard, nanotheranostic is a multipotential single platform for both cancer diagnosis and treatment through enhanced aqueous solubility and bioavailability of the encapsulated agent, stimulus responsiveness, tumor-specific targeting ability, precise tumor imaging, and real-time drug delivery. Nonetheless, the translational success of nanotheranostic platforms is still in its infancy and requires more extensive research in the context of tumor heterogeneity, safety profile, and regulatory issues, which pose one of the largest technological limitations. The present review summarizes different nanotheranostic platforms and nanotheranostic candidates in clinical trials (AGuIX® , NBTXR3, Ferumoxtran, MM-398, EndoTAG-1, etc.), along with disadvantages and challenges to improving cancer diagnosis and treatment. Overall, the concept, platform, and technical knowledge of nanotheranostics are really helpful to academic and pharmaceutical researchers.

Novel approaches are required to address the urgent need to develop lipid-based carriers of paclitaxel (PTX) and other hydrophobic drugs for cancer chemotherapy. Carriers based on cationic liposomes (CLs) with fluid (i.e., chain-melted) membranes (e.g., EndoTAG-1) have shown promise in preclinical and late-stage clinical studies. Recent work found that the addition of a cone-shaped poly(ethylene glycol)-lipid (PEG-lipid) to PTX-loaded CLs (CLs_PTX) promotes a transition to sterically stabilized, higher-curvature (smaller) nanoparticles consisting of a mixture of PEGylated CLs_PTX and PTX-containing fluid lipid nanodiscs (nanodiscs_PTX). These CLs_PTX and nanodiscs_PTX show significantly improved uptake and cytotoxicity in cultured human cancer cells at PEG coverage in the brush regime (10 mol % PEG-lipid). Here, we studied the PTX loading, in vivo circulation half-life, and biodistribution of systemically administered CLs_PTX and nanodiscs_PTX and assessed their ability to induce apoptosis in triple-negative breast-cancer-bearing immunocompetent mice. We focused on fluid rather than solid lipid nanodiscs because of the significantly higher solubility of PTX in fluid membranes. At 5 and 10 mol % of a PEG-lipid (PEG5K-lipid, molecular weight of PEG 5000 g/mol), the mixture of PEGylated CLs_PTX and nanodiscs_PTX was able to incorporate up to 2.5 mol % PTX without crystallization for at least 20 h. Remarkably, compared to preparations containing 2 and 5 mol % PEG5K-lipid (with the PEG chains in the mushroom regime), the particles at 10 mol % (with PEG chains in the brush regime) showed significantly higher blood half-life, tumor penetration, and proapoptotic activity. Our study suggests that increasing the PEG coverage of CL-based drug nanoformulations can improve their pharmacokinetics and therapeutic efficacy.