Nanoparticle-Mediated Mitochondrial Damage Induces Apoptosis in Cancer

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Updated: Mar 21, 2026

An Automated Differential Nuclear Staining Assay for Accurate Determination of Mitocan Cytotoxicity
07:58

An Automated Differential Nuclear Staining Assay for Accurate Determination of Mitocan Cytotoxicity

Published on: May 12, 2020

7.6K

Abhik Mallick1, Piyush More1, Muhammed Muazzam Kamil Syed1

  • 1Department of Chemistry, Indian Institute of Science Education and Research (IISER)-Pune , Pune, 411008, Maharashtra, India.

ACS Applied Materials & Interfaces
|May 11, 2016
PubMed

Insights

Mitochondria-targeting nanoparticles loaded with two drugs overcome cancer drug resistance. These nanoparticles induce mitochondrial damage and apoptosis, showing promise for next-generation cancer therapeutics.

Area of Science:

  • Biochemistry
  • Nanotechnology
  • Oncology

Background:

  • Mitochondrial DNA targeting is a promising chemotherapy strategy.
  • Single-target inhibition leads to drug resistance, and selective mitochondrial targeting is challenging.
  • Developing multi-drug strategies for simultaneous mitochondrial targeting is crucial.

Purpose of the Study:

  • To engineer triphenylphosphine (TPP)-coated nanoparticles (NPs) carrying α-tocopheryl succinate (TOS) and obatoclax (Obt).
  • To investigate the selective delivery of TOS-TPP-Obt-NPs to cancer cell mitochondria.
  • To evaluate the efficacy of TOS-TPP-Obt-NPs in inducing apoptosis and overcoming drug resistance.

Main Methods:

  • Engineered 131.6 nm spherical nanoparticles coated with TPP and loaded with TOS and Obt.
  • Investigated nanoparticle uptake via macropinocytosis, lysosomal escape, and mitochondrial homing over 24 hours.
  • Assessed mitochondrial outer membrane permeabilization (MOMP), Cytochrome C release, and caspase cleavage in HeLa and MDA-MB-231 cells.

Main Results:

  • TOS-TPP-Obt-NPs successfully entered lysosomes, escaped, and localized to mitochondria.
  • NPs triggered MOMP by inhibiting Bcl-2, leading to Cytochrome C release and apoptosis via caspase-9 and caspase-3 cleavage.
  • Demonstrated improved efficacy in HeLa cells and significant efficacy in drug-resistant MDA-MB-231 cells compared to free drugs.

Conclusions:

  • Simultaneous perturbation of diverse mitochondrial targets using multi-drug nanoparticles is a viable strategy.
  • TPP-coated TOS-Obt NPs offer a promising approach for next-generation cancer therapeutics.
  • This strategy effectively induces apoptosis and overcomes drug resistance in cancer cells.
Keywords:
cancermitochondriananoparticleobatoclaxα-tocopheryl succinate

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