Related Experiment Video

Updated: May 9, 2026

An In-House-Built and Light-Emitting-Diode-Based Photodynamic Therapy Device for Enhancing Verteporfin Cytotoxicity in a 2D Cell Culture Model
11:04

An In-House-Built and Light-Emitting-Diode-Based Photodynamic Therapy Device for Enhancing Verteporfin Cytotoxicity in a 2D Cell Culture Model

Published on: January 13, 2023

Chiral Covalent Organic Frameworks Trigger Tumor-Specific Mitophagy via Notch/Mitogen-Activated Protein Kinase

Wen-Xiu Ren1, Jie Feng1, Ya-Nan Zhai1

  • 1College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Shandong Normal University, Jinan250014, P. R. China.

ACS Nano
|May 7, 2026
PubMed

Insights

Chiral covalent organic frameworks (CCOFs) show promise in cancer therapy by inducing cell death through mitochondrial autophagy in a chirality-dependent manner. The (S)-enantiomer demonstrates superior efficacy, highlighting potential for advanced chiral nanomaterials.

Area of Science:

  • Nanomaterials Science
  • Oncology
  • Biochemistry

Background:

  • Chirality is crucial for antitumor strategies, but its role in cellular metabolism and death pathways is not fully understood.
  • This knowledge gap hinders the development of effective chiral nanoplatforms for cancer treatment.

Purpose of the Study:

  • To engineer a chiral covalent organic framework (CCOF) and investigate its antitumor potential.
  • To elucidate the chirality-dependent mechanisms of CCOF's interaction with tumor cells, including metabolism regulation and cell death induction.
  • To explore the enantiomer-dependent performance of CCOF in biological systems and under laser irradiation.

Main Methods:

  • Fabrication of a propargylamine-linked chiral covalent organic framework (CCOF).
  • Assessment of CCOF's cellular uptake, cytotoxicity, and induction of mitochondrial autophagy in tumor cells.
  • High-throughput transcriptomics analysis to identify underlying molecular mechanisms.
  • In vitro and in vivo evaluation of enantiomer-dependent photocatalytic activity and antitumor efficacy under laser irradiation.

Main Results:

  • CCOF exhibits chirality-dependent cellular uptake and induces mitochondrial autophagy, leading to tumor cell death.
  • (S)-DTzP-COF demonstrated greater potency in activating autophagy compared to (R)-DTzP-COF.
  • Transcriptomics revealed CCOF's involvement in the MAPK signaling pathway, with (S)-DTzP-COF also engaging the Notch signaling pathway.
  • The CCOF nanoplatform showed enantiomer-dependent photocatalytic activity and achieved significant antitumor effects in vivo under laser irradiation.

Conclusions:

  • Chiral covalent organic frameworks (CCOFs) offer a promising avenue for cancer therapy.
  • The study uncovers a novel chirality-dependent mechanism of mitochondrial autophagy induction by CCOFs.
  • (S)-DTzP-COF's enhanced activity and specific pathway engagement provide a foundation for designing advanced chiral nanomaterials for biomedical applications.
Keywords:
chiral covalent organic frameworksenantioselectivemitophagyphotodynamic therapytumor

More Related Videos

Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination05:39

Near Infrared Photoimmunotherapy for Mouse Models of Pleural Dissemination

Published on: February 9, 2021

In Vitro and In Vivo Evaluation of Photocontrolled Biologically Active Compounds - Potential Drug Candidates for Cancer Photopharmacology13:17

In Vitro and In Vivo Evaluation of Photocontrolled Biologically Active Compounds - Potential Drug Candidates for Cancer Photopharmacology

Published on: September 29, 2023

Related Concept Videos

Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
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...
Chirality in Nature02:30

Chirality in Nature

Chirality is the most intriguing yet essential facet of nature, governing life’s biochemical processes and precision. It can be observed from a snail shell pattern in a macroscopic world to an amino acid, the minutest building block of life. Most of the snails around the world have right-coiled shells because of the intrinsic chirality in their genes. All the amino acids present in the human body exist in an enantiomerically pure state, except for glycine - the sole achiral amino acid. The...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...