Remote loading paclitaxel–doxorubicin prodrug into liposomes for cancer combination therapy

Abstract

The combination of paclitaxel (PTX) and doxorubicin (DOX) has been widely used in the clinic. However, it remains unsatisfied due to the generation of severe toxicity. Previously, we have successfully synthesized a prodrug PTX- S -DOX (PSD). The prodrug displayed comparable in vitro cytotoxicity compared with the mixture of free PTX and DOX. Thus, we speculated that it could be promising to improve the anti-cancer effect and reduce adverse effects by improving the pharmacokinetics behavior of PSD and enhancing tumor accumulation. Due to the fact that copper ions (Cu 2+ ) could coordinate with the anthracene nucleus of DOX, we speculate that the prodrug PSD could be actively loaded into liposomes by Cu 2+ gradient. Hence, we designed a remote loading liposomal formulation of PSD (PSD LPs) for combination chemotherapy. The prepared PSD LPs displayed extended blood circulation, improved tumor accumulation, and more significant anti-tumor efficacy compared with PSD NPs. Furthermore, PSD LPs exhibited reduced cardiotoxicity and kidney damage compared with the physical mixture of Taxol and Doxil, indicating better safety. Therefore, this novel nano-platform provides a strategy to deliver doxorubicin with other poorly soluble antineoplastic drugs for combination therapy with high efficacy and low toxicity.

Paclitaxel-Based Chemotherapy Targeting Cancer Stem Cells from Mono- to Combination Therapy

“…Therefore, combination chemotherapy was designed with the liposomes encapsulating PSD (PSD LPs) for controlled release. The PSD LPs enhance the accumulation of PSD in the tumor, showing more anti-tumor effects than that of the non-liposomal formulation of PSD [ 174 ].…”

Chemotherapy effect on neglected thyroid carcinoma metastatic to axilla – A case report

“…The regimen used is in accordance with the regimen recommended by the American Thyroid Association (ATA), namely, doxorubicin and paclitaxel. The combination of these two regimens has been used for a wide variety of tumors and has been shown to have a better effect when used monotherapy [3,[9][10][11][12]. The regimen used is in accordance with the regimen recommended by the ATA, namely, doxorubicin and paclitaxel.…”

“…The regimen used is in accordance with the regimen recommended by the ATA, namely, doxorubicin and paclitaxel. The combination of these two regimens has been used for a wide variety of tumors and has been shown to have a better effect when used monotherapy [3,[9][10][11][12].…”

Polymeric Drug Delivery Systems Bearing Cholesterol Moieties: A Review

“…In such a case, the liposome is just a frame or a transporter of the proper working system. Constructing such systems is widespread due to high durability, simplicity of preparation and easy-to-predict behavior [165][166][167][168][169].…”