Related Experiment Video

Updated: Sep 25, 2026

Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles
07:32

Preparation and Characterization of Individual and Multi-drug Loaded Physically Entrapped Polymeric Micelles

Published on: August 28, 2015

11.6K

Lysosome-Instructed Self-Assembly of Amino-Acid-Functionalized Perylene Diimide for Multidrug-Resistant Cancer Cells

Changjoon Keum1, Jiyoung Hong2, Doyeon Kim2

  • 1Department of Chemical and Biomolecular Engineering, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea.

ACS Applied Materials & Interfaces
|March 24, 2021
PubMed

Insights

This study presents perylene diimide derivatives (PDI-AAs) that self-assemble in lysosomes to overcome multidrug resistance (MDR) in cancer cells. This targeted approach enhances anticancer efficacy and selectivity against MDR cancer cells.

Area of Science:

  • Biochemistry
  • Materials Science
  • Oncology

Background:

  • Multidrug resistance (MDR) in cancer cells significantly limits chemotherapy effectiveness.
  • Drug efflux pumps and lysosomal sequestration/exocytosis mechanisms contribute to MDR.
  • Novel strategies are needed to circumvent MDR and improve therapeutic outcomes.

Purpose of the Study:

  • To develop a lysosome-targeted self-assembly strategy using perylene diimide (PDI) derivatives to overcome anticancer drug resistance.
  • To investigate the mechanism of PDI derivatives in inducing apoptosis in MDR cancer cells.
  • To evaluate the efficacy and selectivity of PDI derivatives compared to conventional chemotherapy.

Main Methods:

  • Synthesis of amphiphilic perylene diimide derivatives functionalized with amino acids (PDI-AAs).
  • Investigation of pH-stimulated self-assembly of PDI-AAs within lysosomes.
  • Assessment of lysosomal rupture and cancer cell apoptosis induction.
  • Comparative efficacy studies on multidrug-resistant (MDR) cancer cells versus normal cells and doxorubicin treatment.

Main Results:

  • PDI-AAs self-assembled into fibrous structures within lysosomes, triggered by low pH.
  • Lysosomal rupture and apoptosis were induced in MDR cancer cells.
  • Normal cells showed negligible apoptosis, indicating high selectivity.
  • PDI-AAs demonstrated a 10.7-fold higher anticancer efficacy against MDR cancer cells compared to doxorubicin.
  • Agglomerated PDI-AA assemblies were resistant to lysosomal exocytosis.

Conclusions:

  • Lysosome-targeted self-assembly of PDI-AAs offers a potent strategy to overcome MDR in cancer.
  • PDI-AAs exhibit significant anticancer efficacy and selectivity, making them promising candidates for MDR cancer therapy.
  • The mechanism involves lysosomal rupture induced by self-assembled PDI-AAs, leading to cancer cell death.
Keywords:
cancerlysosomemultidrug resistanceperylene diimideself-assembly

More Related Videos

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid05:08

Solubility of Hydrophobic Compounds in Aqueous Solution Using Combinations of Self-assembling Peptide and Amino Acid

Published on: September 20, 2017

17.3K
Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies08:54

Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies

Published on: February 17, 2023

1.3K

Related Concept Videos

Intralumenal Vesicles and Multivesicular Bodies01:38

Intralumenal Vesicles and Multivesicular Bodies

Intraluminal vesicles (ILVs) are small vesicles 50-80 nm in diameter formed during the maturation of early endosomes. A specialized endosome containing numerous ILVs is called a multivesicular body (MVB). ILVs contain internalized molecules such as antigens, nucleic acids, proteins, and metabolites. Some of these molecules are released from the MVBs inside exosomes and are transported to other cells. Other MVBs contain molecules that are retained in the ILVs and are later degraded within the...
Delivery Pathways to the Lysosome01:36

Delivery Pathways to the Lysosome

Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Autophagy01:27

Autophagy

Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
Lysosomal Hydrolases01:22

Lysosomal Hydrolases

Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However, invadopodia can...
Site-Targeted Drug Delivery Systems: Polymeric Carriers01:24

Site-Targeted Drug Delivery Systems: Polymeric Carriers

Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...