Codelivery of dihydroartemisinin and doxorubicin in mannosylated liposomes for drug-resistant colon cancer therapy

Abstract

Multidrug resistance (MDR) is a major hurdle in cancer chemotherapy and makes the treatment benefits unsustainable. Combination therapy is a commonly used method for overcoming MDR. In this study we investigated the anti-MDR effect of dihydroartemisinin (DHA), a derivative of artemisinin, in combination with doxorubicin (Dox) in drug-resistant human colon tumor HCT8/ADR cells. We developed a tumor-targeting codelivery system, in which the two drugs were co-encapsulated into the mannosylated liposomes (Man-liposomes). The Man-liposomes had a mean diameter of 158.8 nm and zeta potential of -15.8 mV. In the HCT8/ADR cells that overexpress the mannose receptors, the Man-liposomes altered the intracellular distribution of Dox, resulting in a high accumulation of Dox in the nuclei and thus displaying the highest cytotoxicity (IC=0.073 μg/mL) among all the groups. In a subcutaneous HCT8/ADR tumor xenograft model, administration of the Man-liposomes resulted in a tumor inhibition rate of 88.59%, compared to that of 47.46% or 70.54%, respectively, for the treatment with free Dox or free Dox+DHA. The mechanisms underlying the anti-MDR effect of the Man-liposomes involved preferential nuclear accumulation of the therapeutic agents, enhanced cancer cell apoptosis, downregulation of Bcl-xl, and the induction of autophagy.

Co-delivery of dihydroartemisinin and docetaxel in pH-sensitive nanoparticles for treating metastatic breast cancerviathe NF-κB/MMP-2 signal pathway

“…23 DHA mediates cell cycle arrest, induces apoptosis, blocks angiogenesis and inhibits tumor metastasis. 24,25 Furthermore, combining DHA with other chemotherapeutics induces synergetic effects. We thus hypothesized that a combination of DTX and DHA could induce synergistic effects in inhibiting metastasis of breast cancer.…”

Progress in nano-drug delivery of artemisinin and its derivatives: towards to use in immunomodulatory approaches

“…Kang and coworkers developed mannosylated liposomes containing DHA. The nanosystem was able to inhibit tumor growth above 88% in colorectal cancer model, indicating the elevation of the apoptosis phenomenon in tumor lines [38].…”

pH-sensitive polymeric nanoparticles of mPEG-PLGA-PGlu with hybrid core for simultaneous encapsulation of curcumin and doxorubicin to kill the heterogeneous tumour cells in breast cancer

“…The cascading release profiles of two drugs with different therapeutic mechanism may be more in line with the needs of the practical treatment. For example, the treatment of drug-resistant tumours often require a faster release of P-gp inhibitor to increase the concentration of a slower release of chemotherapy drugs in these drug-resistant cells [29,30].…”