Amphiphilic Twin Drug Nanoparticles For Cancer Therapy

Nanotechnology has the potential to revolutionize cancer therapy. Recently, Nanocarriers based on the polymer have been studied extensively and used in chemotherapeutic drugs delivery. Although they can be effective, nanocarriers encounter numerous barriers regarding low drug loading efficiency and short-term or long-term toxicities arising from the synthetic nanomaterials, which lead to the limitations of their use in in clinical.Based on the previous research, we proposed a new concept of self-assembled nanoparticles of amphiphilic twin drug used as the carrier-free nano-drug delivery system. We conjugated the hydrophilic anticancer drug and hydrophobic anticancer drug into an amphiphilic twin drug, which could self-assemble into nanoparticles for cancer therapy. The details are as follows:(1) Self-assembled nanoparticles of amphiphilic twin drug synthesized by irinotecan(Ir) and bendamustine(BdM) applied to overcome MDR. The Ir-BdM twin drug was synthesized via a hydrolyzable ester linkage. The chemical structure was characterized by 1H NMR, 13 C NMR, MS, FTIR and UV-Vis. Due to its inherent amphiphilicity, the Ir-BdM twin drug self-assembled into nanoparticles. The size and morphology of Ir-BdM twin drug nanoparticles were characterized by DLS and TEM. The proliferation inhibition of FdU-BdM twin drug nanoparticles was evaluated against MCF-7 cancer cells and MCF-7/ADR cancer cells by MTT assay.(2) Self-assembled nanoparticles of amphiphilic twin drug from floxuridine(Fd U) and BdM for cancer therapy. The FdU-BdM twin drug was synthesized by esterification, and its chemical structure was characterized by 1H NMR, 13 C NMR, LC-MS, FTIR, UV-Vis and fluorescence spectra in detail. The FdU-BdM twin drug nanoparticles were fabricated in selective solvent. After cellular endocytosis, the ester bond between FdU and BdM was readily cleaved by hydrolysis to release free FdU and BdM. The in vitro release behavior of FdU-BdM twin drug nanoparticles was investigated. Then, the cellular uptake of FdU-BdM twin drug nanoparticles by HeLa cells was evaluated by fluorescence microscopy and flow cytometry. The proliferation inhibition of FdU-BdM twin drug nanoparticles was evaluated against HeLa, MCF-7 cancer cells and MCF-7/ADR cancer cells by MTT assay. Apoptosis of cancer cell induced by FdU-BdM twin drug nanoparticles and the expression of caspase-3 protein activated by FdU-Bd M twin drug nanoparticles were evaluated. The in vitro results show that the FdU-BdM twin drug nanoparticles can overcome the multidrug resistance(MDR) and present an excellent anticancer activity.