1. Sequential administration of sialic acid-modified liposomes as carriers for epirubicin and zoledronate elicit stronger antitumor effects with reduced toxicity.
- Author
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Sui, Dezhi, Tang, Xueying, Ding, Junqiang, Wang, Yang, Qin, Ying, Zhang, Ning, Liu, Xinrong, Deng, Yihui, and Song, Yanzhi
- Subjects
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ZOLEDRONIC acid , *DRUG utilization , *EPIRUBICIN , *DRUG administration , *PHENOTYPIC plasticity , *SALICYLIC acid , *LIPOSOMES - Abstract
[Display omitted] 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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