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Study on the anticarcinogenic effect and acute toxicity of liver-targeting mitoxantrone nanoparticles
Abstract:
AIM:To study the anticarcinogenic effect and acute toxicity of liver targeting mitoxantrone nanospheres.METHODS:The anticarcinogenic effect of mitoxan-trone polybutylcyanoacrylate nanoparticles (DHAQ-PBCA-NP) was investigated by using heterotopic and orthotopic transplantation models of human hepatocellular carcinoma (HCC) in nude mice and was compared with mitoxantrone (DHAQ) and doxorubicin (ADR).The acute toxicity of DHAQ-PBCA-NP lyophilized injection in mice was also studied.RESULTS:The tumor inhibition rates of ADR, DHAQ, DHAQ-PBCA-NP to orthotopically transplanted HCC were 60.07%, 67.49% and 99.44%, respectively, but regard to heterotopically transplanted HCC, these were 80.03%, 86.18% and 92.90%, which were concordant with the results acquired by mitosis counting and proliferating cell nuclear antigen (PCNA). After iv administration to mice with DHAQ-PBCA-NP, the LD(50) was 16.9mg/kg ± 3.9mg/kg, no obvious local irritation was observed and there was no significant damage to the structure of liver cells, and that of the heart, spleen and kidneys.CONCLUSION:The effect of DHAQ-PBCA-NP was significantly higher than that of DHAQ and ADR in the anti orthotopically transplanted HCC and the acute toxicity was relatively low.
Insights
Liver-targeting mitoxantrone nanospheres demonstrated superior anticarcinogenic effects against human hepatocellular carcinoma in mice compared to traditional treatments. These novel nanospheres also exhibited low acute toxicity, indicating a promising therapeutic potential.
Area of Science:
- Oncology
- Nanomedicine
- Pharmacology
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- Developing targeted drug delivery systems can improve treatment efficacy and reduce toxicity.
- Mitoxantrone is an effective chemotherapeutic agent, but its delivery can be optimized.
Purpose of the Study:
- To evaluate the anticarcinogenic efficacy of liver-targeting mitoxantrone polybutylcyanoacrylate nanoparticles (DHAQ-PBCA-NP).
- To assess the acute toxicity profile of DHAQ-PBCA-NP in a preclinical setting.
- To compare the performance of DHAQ-PBCA-NP against mitoxantrone (DHAQ) and doxorubicin (ADR).
Main Methods:
- Utilized heterotopic and orthotopic transplantation models of human HCC in nude mice.
- Administered DHAQ-PBCA-NP, DHAQ, and ADR to assess tumor inhibition rates.
- Conducted mitosis counting and proliferating cell nuclear antigen (PCNA) analysis.
- Determined the LD(50) and evaluated local irritation and organ damage following intravenous administration of DHAQ-PBCA-NP.
Main Results:
- DHAQ-PBCA-NP achieved a 99.44% tumor inhibition rate in orthotopic HCC models, significantly higher than ADR (60.07%) and DHAQ (67.49%).
- In heterotopic models, DHAQ-PBCA-NP showed 92.90% inhibition, compared to 80.03% for ADR and 86.18% for DHAQ.
- The LD(50) of DHAQ-PBCA-NP was 16.9mg/kg ± 3.9mg/kg, with no significant local irritation or damage to major organs observed.
Conclusions:
- Liver-targeting mitoxantrone nanospheres (DHAQ-PBCA-NP) exhibit significantly enhanced anticarcinogenic effects against orthotopic HCC compared to DHAQ and ADR.
- DHAQ-PBCA-NP demonstrates a favorable safety profile with relatively low acute toxicity.
- These findings suggest DHAQ-PBCA-NP holds considerable promise as a targeted therapy for hepatocellular carcinoma.