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Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Nano-mupirocin as tumor-targeted antibiotic: Physicochemical, immunotoxicological and pharmacokinetic
Ahuva Cern1, Sarah L Skoczen2, Kelsie S Snapp2
1Laboratory of Membrane and Liposome Research, Department of Biochemistry, The Hebrew University of Jerusalem, Israel.
Abstract:
Nano-mupirocin is a PEGylated nano-liposomal formulation of the antibiotic mupirocin, undergoing evaluation for treating infectious diseases and intratumor bacteria. Intratumoral microbiota play an important role in the regulation of tumor progression and therapeutic efficacy. However, antibiotic use to target intratumoral bacteria should be performed in a way that will not affect the gut microbiota, found to enable the efficacy of cancer treatments. Nano-mupirocin may offer such a selective treatment. Herein, we demonstrate the ability of Nano-mupirocin to successfully target tumor-residing Fusobacterium nucleatum without an immediate effect on the gut microbiome. In-depth characterization of this novel formulation was performed, and the main findings include: (i). the pharmacokinetic analysis of mupirocin administered as Nano-mupirocin vs mupirocin lithium (free drug) demonstrated that most of the Nano-mupirocin in plasma is liposome associated; (ii). microbiome analysis of rat feces showed no significant short-term difference between Nano-mupirocin, mupirocin lithium and controls; (iii). Nano-mupirocin was active against intratumoral F. nucleatum, a tumor promoting bacteria that accumulates in tumors of the AT3 mice model of breast cancer. These data suggest the ability of Nano-mupirocin to target tumor residing and promoting bacteria.
Insights
Nano-mupirocin, a novel liposomal antibiotic, effectively targets tumor bacteria like Fusobacterium nucleatum without harming gut microbes. This selective approach may improve cancer treatment efficacy by preserving beneficial gut microbiota.
Area of Science:
- Oncology
- Microbiology
- Pharmacology
Background:
- Intratumoral microbiota influence tumor progression and cancer treatment outcomes.
- Antibiotic strategies targeting intratumoral bacteria must avoid disrupting beneficial gut microbiota.
- Nano-mupirocin is a PEGylated nano-liposomal formulation of mupirocin designed for selective bacterial targeting.
Purpose of the Study:
- To evaluate Nano-mupirocin's ability to target intratumoral Fusobacterium nucleatum.
- To assess the short-term impact of Nano-mupirocin on gut microbiome composition.
- To characterize the pharmacokinetics and intratumoral activity of Nano-mupirocin.
Main Methods:
- Pharmacokinetic analysis comparing Nano-mupirocin and mupirocin lithium.
- Fecal microbiome analysis in rats treated with Nano-mupirocin, mupirocin lithium, or controls.
- Assessment of Nano-mupirocin activity against intratumoral F. nucleatum in a breast cancer mouse model.
Main Results:
- Pharmacokinetic studies showed Nano-mupirocin predominantly remained liposome-associated in plasma.
- No significant short-term differences in gut microbiome composition were observed between Nano-mupirocin, mupirocin lithium, and control groups.
- Nano-mupirocin demonstrated activity against intratumoral F. nucleatum in the AT3 mice model.
Conclusions:
- Nano-mupirocin selectively targets tumor-residing bacteria, including Fusobacterium nucleatum.
- This formulation exhibits minimal immediate impact on the gut microbiome.
- Nano-mupirocin holds potential for treating infections and modulating intratumoral bacteria in cancer therapy.
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