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A Tween-80 modified hypoxia/esterase dual stimulus-activated nanomicelle as a delivery platform for carmustine -

Duo Li1, Ting Ren1, Xiaoli Wang1

  • 1Beijing Key Laboratory of Environmental & Viral Oncology, College of Chemistry and Life Science, Beijing University of Technology, Beijing 100124, China.

International Journal of Biological Macromolecules
|June 26, 2024
PubMed

Insights

This study developed novel nanomicelles loaded with carmustine (BCNU) to overcome drug resistance and the blood-brain barrier (BBB) for glioma treatment. The T80-HACB/BCNU NPs demonstrated enhanced anti-glioma efficacy and improved BBB transport.

Area of Science:

  • Nanomedicine
  • Drug Delivery
  • Oncology

Background:

  • Carmustine (BCNU) efficacy for glioma is limited by drug resistance (O6-alkylguanine-DNA alkyltransferase) and the blood-brain barrier (BBB).
  • Novel nanocarrier systems are needed to enhance BCNU delivery and overcome resistance mechanisms in brain tumors.

Purpose of the Study:

  • To synthesize and characterize BCNU-loaded nanomicelles (T80-HACB/BCNU NPs) designed for dual-stimulus (hypoxia/esterase) activation.
  • To evaluate the enhanced transport across the BBB and improved anti-glioma cytotoxicity of the developed nanomicelles.

Main Methods:

  • Synthesis of T80-HACB/BCNU NPs with Tween 80 coating for BBB transport and hyaluronic acid-linked hypoxia-sensitive inhibitors.
  • Characterization of particle size, zeta potential, drug loading capacity, and in vitro drug release kinetics.
  • Assessment of cytotoxicity against hypoxic glioma cells (T98G, SF763) and evaluation of BBB transport using an in vitro model.

Main Results:

  • T80-HACB/BCNU NPs exhibited a particle size of 232.10 ± 10.66 nm and zeta potential of -18.13 ± 0.91 mV with high drug loading.
  • Enhanced cytotoxicity was observed against hypoxic glioma cells, with IC50 values around 132-133 μM.
  • Tween 80 modification significantly improved in vitro BBB transport, showing a 7.6-fold increase compared to unmodified micelles.

Conclusions:

  • The developed T80-HACB/BCNU NPs effectively overcome BCNU resistance and BBB limitations.
  • This dual-stimulus responsive nanomicelle system holds promise for developing advanced and highly effective chemotherapy strategies for gliomas.
Keywords:
CarmustineHypoxia/esterase-responsive nano-micelleTarget delivery

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