Sequential administration of sialic acid-modified liposomes as carriers for epirubicin and zoledronate elicit stronger antitumor effects with reduced toxicity.
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| Abstract |
Combined administration of drugs can improve efficacy and reduce toxicity; therefore, this combination approach has become a routine method in cancer therapy. The main combination regimens are sequential, mixed (also termed "cocktail"), and co-loaded; however, other combinations, such as administration of synergistic drugs and the use of formulations with different mechanisms of action, may exert better therapeutic effects. Tumor-associated macrophages (TAMs) play functional roles throughout tumor progression and exhibit characteristic phenotypic plasticity. Sialic acid (SA)-modified epirubicin liposomes (S-E-L) and SA-modified zoledronate liposomes (S-Z-L) administered separately kill TAMs, reverse their phenotype, and achieve antitumor effects. In this study, we examined the effects of a two-treatment combination for drug delivery, using sequential, mixed, and co-loaded drug delivery. We found that therapeutic effects differed between administration methods: mixed administration of S-E-L and S-Z-L, co-loaded administration of SA-modified liposomes (S-ZE-C), and sequential administration of S-E-L injected 24 h after S-Z-L did not inhibit tumor growth; however, sequential administration of S-Z-L injected 24 h after S-E-L resulted in no tumor growth, no toxicity to noncancerous tissue, and no death of mice, and exhibited 25% tumor shedding. Thus, our results thus encourage the further development of combined therapies for nanomedicines based on the mechanisms investigated here.
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| Authors | Dezhi Sui, Xueying Tang, Junqiang Ding, Yang Wang, Ying Qin, Ning Zhang, Xinrong Liu, Yihui Deng, Yanzhi Song |
| Journal | International journal of pharmaceutics (Int J Pharm) Vol. 602 Pg. 120552 (Jun 01 2021) ISSN: 1873-3476 [Electronic] Netherlands |
| PMID | 33798685 (Publication Type: Journal Article) |
| Copyright | Copyright © 2021 Elsevier B.V. All rights reserved. |
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