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Macroporous silica nanoparticles for delivering Bcl2-function converting peptide to treat multidrug resistant-cancer

Weixia Xu1, Pengjin Ge1, Boning Niu1

  • 1School of Pharmaceutical Sciences, and Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiang'an South Road, Xiamen, Fujian 361102, China.

Journal of Colloid and Interface Science
|May 23, 2018
PubMed

Insights

Researchers developed macroporous silica nanoparticles to deliver a peptide that converts cancer-protective Bcl-2 into a killer. This novel drug delivery platform effectively treats multidrug-resistant cancer cells by enhancing peptide delivery and efficacy.

Area of Science:

  • Biomaterials Science
  • Nanotechnology
  • Cancer Biology

Background:

  • B cell lymphoma gene 2 (Bcl-2) promotes cancer cell survival and chemoresistance.
  • A peptide from orphan nuclear receptor Nur77 can reverse Bcl-2's function, turning it into a cancer cell killer.
  • Efficient delivery of therapeutic peptides to cancer cells remains a significant challenge, especially with traditional small-pore nanoparticles.

Purpose of the Study:

  • To engineer a novel delivery platform for a Bcl-2-converting peptide.
  • To overcome limitations of small-pore mesoporous silica nanoparticles for peptide delivery.
  • To investigate the role of pore size and surface functionality in nanoparticle-mediated peptide delivery for treating multidrug-resistant cancer.

Main Methods:

  • Fabrication of macroporous silica nanoparticles (MSNs) with tunable pore sizes and surface functionalities.
  • Modification of MSNs with thiol and amine groups to enhance peptide loading and cellular uptake.
  • Evaluation of peptide encapsulation efficiency and intracellular delivery into MCF7/DOX cancer cells.
  • Assessment of peptide-induced apoptosis via mitochondrial targeting and Bcl-2 BH3 domain exposure.

Main Results:

  • Macroporous silica nanoparticles demonstrated high peptide-loading efficiency (>40%), particularly with thiol modification.
  • Surface-functionalized MSNs facilitated peptide penetration into cancer cells and mitochondria.
  • The peptide successfully bound to Bcl-2, exposing the BH3 domain and inducing apoptosis.
  • Amine-modified MSNs showed a pronounced effect on peptide-induced apoptosis compared to other modifications.

Conclusions:

  • Engineered macroporous silica nanoparticles provide an effective platform for delivering Bcl-2-converting peptides.
  • Tuning nanoparticle pore size and surface functionality is crucial for efficient delivery of biomacromolecules.
  • This approach offers a promising strategy for treating multidrug-resistant cancers with elevated Bcl-2 levels.
Keywords:
Bcl-2-converting peptideIntracellular deliveryMacroporous silica nanoparticlesMultidrug resistanceSurface functionality

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