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Co-delivery of a RanGTP inhibitory peptide and doxorubicin using dual loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer cells
Haggag, Y. Abu Ras, Bayan El-Tanani, Yahia Tambuwala, M.M. McCarron, P. Isreb, Mohammad El-Tanani, Mohamed
Haggag, Y.
Abu Ras, Bayan
El-Tanani, Yahia
Tambuwala, M.M.
McCarron, P.
Isreb, Mohammad
El-Tanani, Mohamed
Publication Date
2020-11
End of Embargo
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© 2020 Taylor & Francis. This is an Author's Original Manuscript of an article published by Taylor & Francis in Expert Opinion on Drug Delivery on 15 Sep 2020 available online at https://doi.org/10.1080/17425247.2020.1813714.
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openAccess
Accepted for publication
19/08/2020
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Abstract
Multidrug resistance (MDR) limits the beneficial outcomes of conventional breast cancer chemotherapy. Ras-related nuclear protein (Ran-GTP) plays a key role in these resistance mechanisms, assisting cancer cells to repair damage to DNA. Herein, we investigate the co-delivery of Ran-RCC1 inhibitory peptide (RAN-IP) and doxorubicin (DOX) to breast cancer cells using liposomal nanocarriers.
A liposomal delivery system, co-encapsulating DOX, and RAN-IP, was prepared using a thin-film rehydration technique. Dual-loaded liposomes were optimized by systematic modification of formulation variables. Real-Time-Polymerase Chain Reaction was used to determine Ran-GTP mRNA expression. In vitro cell lines were used to evaluate the effect of loaded liposomes on the viability of breast and lung cancer cell lines. In vivo testing was performed on a murine Solid Ehrlich Carcinoma model.
RAN-IP reversed the Ran-expression-mediated MDR by inhibiting the Ran DNA damage repair function. Co-administration of RAN-IP enhanced sensitivity of DOX in breast cancer cell lines. Finally, liposome-mediated co-delivery with RAN-IP improved the anti-tumor effect of DOX in tumor-bearing mice when compared to single therapy.
This study is the first to show the simultaneous delivery of RAN-IP and DOX using liposomes can be synergistic with DOX and lead to tumor regression in vitro and in vivo.
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Accepted manuscript
Citation
Haggag Y, Abu Ras B, El-Tanani Y et al (2020) Co-delivery of a RanGTP inhibitory peptide and doxorubicin using dual loaded liposomal carriers to combat chemotherapeutic resistance in breast cancer cells. Expert Opinion on Drug Delivery. 17(11): 1655-1669.
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Article