Related Experiment Video

Updated: Apr 12, 2026

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen
19:44

Enhancement of Apoptotic and Autophagic Induction by a Novel Synthetic C-1 Analogue of 7-deoxypancratistatin in Human Breast Adenocarcinoma and Neuroblastoma Cells with Tamoxifen

Published on: May 30, 2012

19.3K

Mitochondria apoptosis pathway synergistically activated by hierarchical targeted nanoparticles co-delivering siRNA

Bing-Feng Zhang1, Lei Xing2, Peng-Fei Cui2

  • 1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, PR China; College of Chemistry and Bio-engineering, Yichun University, Yichun 336000, PR China.

Biomaterials
|May 26, 2015
PubMed

Insights

This study developed a novel nanoparticle system to deliver siRNA and chemotherapy drugs, enhancing cancer cell apoptosis by targeting mitochondria and overcoming drug resistance. This approach shows promise for more effective cancer treatment.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Mitochondria-mediated apoptosis is a key cancer therapy target.
  • Overexpressed anti-apoptotic proteins like Bcl-2 hinder chemotherapy efficacy.
  • Targeted delivery systems are needed to overcome apoptosis evasion in cancer cells.

Purpose of the Study:

  • To construct a hierarchical targeted delivery system for sequential delivery of siRNA and chemotherapeutic agents.
  • To enhance the efficacy of mitochondria-mediated apoptosis for cancer therapy.
  • To overcome cancer cell resistance to apoptosis.

Main Methods:

  • Synthesis of TPP-CP-LND (TCPL) copolymer incorporating a mitochondria-targeting ligand (TPP) and lonidamine (LND).
  • Complexation of TCPL with siRNA and subsequent coating with PPF copolymer to form hierarchical targeted nanoparticles (TCPL/siRNA/PPF NPs).
  • Evaluation of nanoparticle characteristics, stability, pH-responsive release, and in-vitro therapeutic efficacy.

Main Results:

  • TCPL/siRNA/PPF NPs demonstrated neutral surface charge, plasma stability, and pH-responsive shell separation.
  • The nanoparticles achieved simultaneous release of siBcl-2 into the cytoplasm and LND delivery to mitochondria within the same cancer cell.
  • Synergistic activation of the mitochondria apoptosis pathway was observed, leading to enhanced cancer cell death.

Conclusions:

  • The developed hierarchical targeted co-delivery system effectively stimulates the mitochondria apoptosis pathway.
  • Combining RNA interference (siBcl-2) with mitochondria-targeted chemotherapy (LND) offers a synergistic approach for cancer treatment.
  • This strategy holds significant potential for improving cancer therapy by overcoming apoptosis resistance.
Keywords:
Co-deliveryHierarchical targetingLonidamineMitochondria apoptosis pathwayMultifunctional nanoparticlesiRNA

More Related Videos

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells07:23

Dual CRISPR-Interference Strategy for Targeting Synthetic Lethal Interactions Between Non-Coding RNAs in Cancer Cells

Published on: May 30, 2025

1.3K
Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro13:20

Detection of Mitochondria Membrane Potential to Study CLIC4 Knockdown-induced HN4 Cell Apoptosis In Vitro

Published on: July 17, 2018

10.9K

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
9.3K
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size...
17.1K
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
9.4K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
19.7K
Autophagic Cell Death01:18

Autophagic Cell Death

Christian de Duve discovered “autophagy,” a process in which cellular components are engulfed by membrane-bound organelles called autophagosomes. The autophagosomes then fuse with lysosomes to digest the enclosed contents. Autophagy is generally activated in cells to prevent cell death. However, cell death is triggered when the damage is beyond repair.
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and...
5.1K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
6.4K