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Purpose <p>Glioblastoma multiforme (GBM) is an aggressive malignancy with poor prognosis and high morbidity, primarily due to the blood-brain barrier (BBB) limiting the effectiveness of standard chemotherapy. We developed a dual-ligand liposome-based drug delivery system to overcome this challenge by enhancing tumor targeting. Our approach utilizes liposomes loaded with temozolomide (TMZ) and O6-benzylguanine (O6-BG) and conjugated with transferrin and anti-integrin antibodies, enabling them to cross the BBB and deliver drugs directly to the tumor site.</p> Methods <p>The thin-layer hydration method was employed to prepare ligand-functionalized liposomes. Compared to the free drug combination, the cytotoxic potential of liposomes was estimated using MTT and apoptosis assays. A radioisotope was tagged to assess plasma, brain, and organ distribution in nude mice. Non-invasive bioluminescence imaging was utilized to visualize tumor response.</p> Results <p>The optimized nanovesicles (187.4 ± 6.5&#xa0;nm) exhibited prolonged drug release in tumors, contributing to cell death, as demonstrated through in vitro studies. The drug synergistic effect (combination index: 0.3) resulted in a 1.75- and 3.45-fold increase in cytotoxicity against GBM cells compared to the free drug combinations. Gamma scintigraphy indicated prolonged retention at the tumor site with minimal distribution to other vital organs post-12&#xa0;h treatment. Despite a reduced dose of TMZ, this unique nanoliposome achieved a two-fold reduction in tumor size, as evidenced by a corresponding decrease in the cell proliferation index.</p> Conclusion <p>This study opens new avenues for enhancing the therapeutic efficacy of drug combinations by optimizing cellular targeting while significantly decreasing systemic toxicity.</p>

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Exploring anti-integrin α6 antibody and transferrin-decorated dual drug-loaded liposomes as a promising nanoplatform for glioblastoma therapy: a preclinical approach

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月22日

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  • Manasa Manjunath Hegde,
  • Jayant Sastri Goda,
  • Srinivas Mutalik,
  • Pranoti Palkar,
  • Bhabani Shankar Mohanty,
  • Pradip Chaudhari,
  • Ayushi Sahay,
  • Rahul Thorat,
  • Guruprasad Kanive Parashiva,
  • Bola Sadashiva Satish Rao

摘要

Purpose

Glioblastoma multiforme (GBM) is an aggressive malignancy with poor prognosis and high morbidity, primarily due to the blood-brain barrier (BBB) limiting the effectiveness of standard chemotherapy. We developed a dual-ligand liposome-based drug delivery system to overcome this challenge by enhancing tumor targeting. Our approach utilizes liposomes loaded with temozolomide (TMZ) and O6-benzylguanine (O6-BG) and conjugated with transferrin and anti-integrin antibodies, enabling them to cross the BBB and deliver drugs directly to the tumor site.

Methods

The thin-layer hydration method was employed to prepare ligand-functionalized liposomes. Compared to the free drug combination, the cytotoxic potential of liposomes was estimated using MTT and apoptosis assays. A radioisotope was tagged to assess plasma, brain, and organ distribution in nude mice. Non-invasive bioluminescence imaging was utilized to visualize tumor response.

Results

The optimized nanovesicles (187.4 ± 6.5 nm) exhibited prolonged drug release in tumors, contributing to cell death, as demonstrated through in vitro studies. The drug synergistic effect (combination index: 0.3) resulted in a 1.75- and 3.45-fold increase in cytotoxicity against GBM cells compared to the free drug combinations. Gamma scintigraphy indicated prolonged retention at the tumor site with minimal distribution to other vital organs post-12 h treatment. Despite a reduced dose of TMZ, this unique nanoliposome achieved a two-fold reduction in tumor size, as evidenced by a corresponding decrease in the cell proliferation index.

Conclusion

This study opens new avenues for enhancing the therapeutic efficacy of drug combinations by optimizing cellular targeting while significantly decreasing systemic toxicity.