Exceedingly Higher co-loading of Curcumin and Paclitaxel onto Polymer-functionalized Reduced Graphene Oxide for Highly Potent Synergistic Anticancer Treatment

Abstract

Metastasis of lung carcinoma to breast and vice versa accounts for one of the vast majority of cancer deaths. Synergistic treatments are proven to be the effective method to inhibit malignant cell proliferation. It is highly advantageous to use the minimum amount of a potent toxic drug, such as paclitaxel (Ptx) in ng/ml together with a natural and safe anticancer drug, curcumin (Cur) to reduce the systemic toxicity. However, both Cur and Ptx suffer from poor bioavailability. Herein, a drug delivery cargo was engineered by functionalizing reduced graphene oxide (G) with an amphiphilic polymer, PF-127 (P) by hydrophobic assembly. The drugs were loaded via pi-pi interactions, resulting in a nano-sized GP-Cur-Ptx of 140 nm. A remarkably high Cur loading of 678 wt.% was achieved, the highest thus far compared to any other Cur nanoformulations. Based on cell proliferation assay, GP-Cur-Ptx is a synergistic treatment (CI < 1) and is highly potent towards lung, A549 (IC50 = 13.24 μg/ml) and breast, MDA-MB-231 (IC50 = 1.450 μg/ml) cancer cells. These positive findings are further confirmed by increased reactive oxygen species, mitochondrial membrane potential depletion and cell apoptosis. The same dose treated on normal MRC-5 cells shows that the system is biocompatible and cancerous cell-specific.

Cardiac glycoside sensitized hepatocellular carcinoma cells to TRAIL via ROS generation, p38MAPK, mitochondrial transition, and autophagy mediation

“…Furthermore, Bcl‐2 family member proteins, including proapoptotic (eg, Bax, Bak, Bad, and Bid) and antiapoptotic members (eg, Bcl‐2, Bcl‐xL, and Mcl‐1) regulated the mitochondrial outer membrane permeability, thus governing the intrinsic pathway of cell death, which is referred to as the mitochondrial pathway. The activation of cytotoxic stimuli through ROS or other tumor suppressors indicate the release of proapoptotic proteins from the mitochondria including cytochrome c, thereby inducing mitochondrial permeability transition, which is associated with a decrease in MMP . The generation of ROS, however, may result in an imbalance in the intracellular redox status, which then allows ROS to mediate MMP transition, mitochondrial release of cytochrome c into the cytosol, and caspase activation.…”

“…tion, which is associated with a decrease in MMP. 45 The generation of ROS, however, may result in an imbalance in the intracellular redox status, which then allows ROS to mediate MMP transition, mitochondrial release of cytochrome c into the cytosol, and caspase activation. The proapoptotic Bax protein induces mitochondrial dysfunction and cytochrome c release from the mitochondrion that interacts with a specific adapter, which in turn activates pro-caspases to active caspases.…”

Graphenic Materials for Biomedical Applications

“…The terms GBMs or graphene family nanomaterial (GFNs) includes GR and its derivatives, such as GO, rGO, GR/GO dots (GD/GOD), GR nano-onions, and GR nano-ribbons, as well as fullerenes, and CNTs, see Figure 2 [10,11]. groups, while at the edges of the flakes there are carboxylic groups [18,22,23].…”

Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors

“…108 Metastasis of lung tumor cells to a secondary location such as breast and vice versa accounts for the vast majority of tumor deaths and presents a major challenge in cancer treatment. 143 One of the main problems of existing chemotherapy for lung tumor is its inadequate efficiency and specificity. Thus, it is always required to develop site-specific and targeted therapies to attain adequate efficacy and reduced side effects.…”