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Updated: Oct 23, 2025
Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
Published on: August 2, 2016
RVG-functionalized reduction sensitive micelles for the effective accumulation of doxorubicin in brain
Jiangkang Xu1, Xiaoye Yang1, Jianbo Ji1
1Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, People's Republic of China.
Background:
Glioblastoma is a lethal neoplasm with few effective therapy options. As a mainstay in the current treatment of glioma at present, chemotherapeutic agents usually show inadequate therapeutic efficiency due to their low blood brain barrier traversal and brain targeting, together with tumor multidrug resistance. Novel treatment strategies are thus urgently needed to improve chemotherapy outcomes.
Results:
Here, we report that nanomedicines developed by functionalizing the neurotropic rabies virus-derived polypeptide, RVG, and loading reduction-sensitive nanomicelles (polymer and doxorubicin) enable a highly specific and efficacious drug accumulation in the brain. Interestingly, curcumin serves as the hydrophobic core of the polymer, while suppressing the major efflux proteins in doxorubicin-resistant glioma cells. Studies on doxorubicin-resistant rat glioma cells demonstrate that the RVG-modified micelles exhibit superior cell entry and antitumor activity. In vivo research further showed that RVG modified nanomicelles significantly enhanced brain accumulation and tumor inhibition rate in mice, leading to a higher survival rate with negligible systemic toxicity. Moreover, effective suppression of recurrence and pulmonary metastatic nodules were also determined after the RVG-modified nanomicelles treatment.
Conclusions:
The potential of RVG-modified nanomicelles for glioma was demonstrated. Brain accumulation was markedly enhanced after intravenous administration. This unique drug delivery nanoplatform to the brain provides a novel and powerful therapeutic strategy for the treatment of central nervous system disorders including glioma.
Insights
Novel RVG-modified nanomicelles effectively target the brain, enhancing chemotherapy for glioblastoma. This nanomedicine approach improves drug delivery, boosts antitumor activity, and increases survival rates with minimal toxicity.
Area of Science:
- Neuroscience
- Oncology
- Nanomedicine
Background:
- Glioblastoma treatment faces challenges due to poor drug delivery across the blood-brain barrier and multidrug resistance.
- Current chemotherapy for glioma has limited efficacy, necessitating innovative therapeutic strategies.
Purpose of the Study:
- To develop and evaluate RVG-modified nanomicelles for enhanced brain drug delivery and glioblastoma treatment.
- To investigate the efficacy of curcumin-loaded, reduction-sensitive nanomicelles functionalized with RVG in overcoming drug resistance.
Main Methods:
- Development of RVG-functionalized, curcumin-loaded, reduction-sensitive nanomicelles encapsulating doxorubicin.
- In vitro studies using doxorubicin-resistant rat glioma cells to assess cell entry and antitumor activity.
- In vivo studies in mice to evaluate brain accumulation, tumor inhibition, survival rates, and systemic toxicity.
Main Results:
- RVG-modified nanomicelles demonstrated superior cell entry and antitumor activity in resistant glioma cells.
- Significant enhancement of brain drug accumulation and tumor inhibition was observed in vivo.
- Treatment led to increased survival rates, suppressed recurrence, reduced metastasis, and showed negligible systemic toxicity.
Conclusions:
- RVG-modified nanomicelles represent a promising drug delivery platform for glioblastoma treatment.
- This nanoplatform significantly enhances brain accumulation, offering a novel therapeutic strategy for central nervous system disorders.
- The approach holds potential for improving chemotherapy outcomes in glioma patients.
