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Updated: Jul 31, 2026
Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
Published on: June 13, 2014
Synthesis and characterization of the tumor targeting mitoxantrone-insulin conjugate
Wen-Sheng Liu1, Yuan Huang, Zhi-Rong Zhang
1Key Laboratory of Drug Targeting and Novel Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu 610041, PR China.
Abstract:
Anticancer drugs have serious side effects arising from their poor malignant cells selectivity. Since insulin receptors highly express on the cytomembrane of some kind of tumor cells, using insulin as the vector was expected to reduce serious side effects of the drugs. The objective of this study was to evaluate the tumor targeting effect of the newly synthesized mitoxantrone-insulin conjugate (MIT-INS) with the drug loading of 11.68%. In vitro stability trials showed MIT-INS were stable in buffers with different pH (2-8) at 37 degrees C within 120 h (less than 3% of free MIT released), and were also stable in mouse plasma within 48 h (less than 1% of free MIT released). In vivo study on tumor-bearing mice showed that, compared with MIT [75.92 microg x h/g of the area under the concentration-time curve (AUC) and 86.85 h of mean residence time (MRT)], the conjugates had better tumor-targeting efficiency with enhanced tumor AUC of 126.53 microg x h/g and MTR of 151.95 h. The conjugate had much lower toxicity to most other tissues with targeting indexes (TIC) no larger than 0.3 besides good tumor targeting efficiency with TIC of 1.67. The results suggest the feasibility to promote the curative effect in cancer chemotherapy by using insulin as the vector of anti-cancer drugs.
Insights
Researchers developed a novel mitoxantrone-insulin conjugate (MIT-INS) for cancer therapy. This drug delivery system enhances tumor targeting and reduces side effects, showing promise for improved chemotherapy outcomes.
Area of Science:
- Oncology
- Drug Delivery Systems
- Bioconjugation
Background:
- Anticancer drugs often cause severe side effects due to low selectivity for malignant cells.
- Insulin receptors are overexpressed on certain tumor cells, presenting a potential target for drug delivery.
Purpose of the Study:
- To synthesize and evaluate a mitoxantrone-insulin conjugate (MIT-INS) for targeted cancer chemotherapy.
- To assess the in vitro stability and in vivo tumor-targeting efficacy of the MIT-INS conjugate.
Main Methods:
- Synthesis of mitoxantrone-insulin conjugate (MIT-INS) with 11.68% drug loading.
- In vitro stability testing in various pH buffers and mouse plasma.
- In vivo pharmacokinetic and biodistribution studies in tumor-bearing mice.
Main Results:
- MIT-INS demonstrated excellent stability in vitro (pH 2-8, 120h) and in mouse plasma (48h).
- In vivo studies showed enhanced tumor targeting efficiency for MIT-INS compared to free mitoxantrone (AUC: 126.53 vs 75.92 μg·h/g; MRT: 151.95 vs 86.85 h).
- The conjugate exhibited significantly lower toxicity to non-target tissues (TIC ≤ 0.3) while maintaining high tumor targeting (TIC = 1.67).
Conclusions:
- Insulin can effectively serve as a drug vector for targeted delivery of anticancer agents.
- The MIT-INS conjugate shows feasibility for improving cancer chemotherapy efficacy and reducing systemic toxicity.
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