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Hypoxia-responsive pullulan-based nanoparticles as erlotinib carriers.

Hriday Bera1, Mohammed A Abosheasha2, Yoshihiro Ito3

  • 1Nano Medical Engineering Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.

International Journal of Biological Macromolecules
|October 2, 2021
PubMed
Summary

A novel hypoxia-responsive polymer nanoparticle effectively delivers erlotinib (ERL) to cervical cancer cells. This targeted approach enhances drug efficacy by releasing ERL under hypoxic conditions, suppressing tumor growth and inducing apoptosis.

Keywords:
Cervical cancerDrug deliveryGraftingHypoxiaNitroimidazoleSuccinyl pullulan

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Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Cancer Therapeutics

Background:

  • Cervical cancer treatment faces challenges with drug delivery and efficacy.
  • Hypoxia is a common characteristic of solid tumors, influencing treatment response.
  • Developing targeted drug delivery systems can improve therapeutic outcomes.

Purpose of the Study:

  • To synthesize and characterize a hypoxia-responsive pullulan-based copolymer for targeted erlotinib (ERL) delivery.
  • To evaluate the efficacy of ERL-loaded nanoparticles (NPs) in cervical cancer cells.
  • To investigate the drug release kinetics and cellular uptake mechanisms of the developed NPs.

Main Methods:

  • Synthesis and structural characterization of succinyl pullulan-g-6-(2-nitroimidazole) hexylamine (Pull-SA-HA-NI).
  • Preparation and characterization of ERL-loaded nanoparticles (NPs), including drug-trapping efficiency (DEE), zeta potential, and diameter.
  • In vitro assessment of drug release under hypoxic and normoxic conditions.
  • Investigation of cellular internalization pathways in HeLa cells.
  • Evaluation of ERL-loaded NPs' effect on HeLa cell proliferation and apoptosis.

Main Results:

  • The hypoxia-responsive copolymer (Pull-SA-HA-NI) showed altered self-assembled structures under hypoxia compared to the control.
  • ERL-loaded NPs exhibited high drug-trapping capacity (94.23%) and favorable physicochemical properties (size: 84.10 nm, zeta potential: +39.21 mV).
  • NPs demonstrated faster ERL release under hypoxic conditions and were internalized via energy-dependent endocytosis.
  • ERL-loaded NPs significantly suppressed HeLa cell proliferation and induced apoptosis more effectively than free ERL.

Conclusions:

  • A novel hypoxia-responsive pullulan-based copolymer nanoparticle system for targeted erlotinib delivery was successfully developed.
  • The developed NPs show promise for enhanced cervical cancer therapy due to hypoxia-triggered drug release and improved cellular effects.
  • This targeted nanodelivery system offers a potential strategy to overcome limitations of conventional chemotherapy for cervical cancer.