ArticleJournal of the American Chemical Society2016
Integrating Enzymatic Self-Assembly and Mitochondria Targeting for Selectively Killing Cancer Cells without Acquired Drug Resistance.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 304 citations in OpenAlex.
- Evaluating Alkaline Phosphatase-Instructed Self-Assembly of d‑Peptide Diesters for Selectively Inhibiting Immunosuppressive Cancer Cells.ACS omega · 2026Article
- Dual-responsive peptide nanoplatform for improved lung cancer therapy via the synergistic suppression of autophagy and drug efflux.Materials today. Bio · 2026Article
- Escape from cell uptake: Drug-Free cancer therapeutics regulated by hydrophobicity and negative charge.Materials today. Bio · 2026Article
- Photoswitchable Peptides as Molecular Tools to Encode Structural Order and Disorder in Intracellular Assemblies.Angewandte Chemie (International ed. in English) · 2026Article
- Bone homeostasis regulation by in vivo generation of osteoclast-derived apoptotic bodies using targeted self-assembly.Nature communications · 2025Article
- Enzyme-Instructed Self-Assembly for Cellular Supramolecular Chemistry.Chemistry, an Asian journal · 2025Review
- Intracellular Peptide N-Myristoylation for Cancer Cell Ferroptosis without Acquired Resistance.Journal of the American Chemical Society · 2025Article
- Targeting Subcellular Organelles in Breast Cancer with Enzyme Induced Self-Assembly: Stimulated Response with Eyes-Absence Enzymes (EYA).Molecular pharmaceutics · 2025Article
- Article
- Organelle-Specific Smart Supramolecular Materials for Bioimaging and Theranostics Application.Topics in current chemistry (Cham) · 2024Review
- Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes.International journal of molecular sciences · 2024Review
- Inhalable SPRAY nanoparticles by modular peptide assemblies reverse alveolar inflammation in lethal Gram-negative bacteria infection.Science advances · 2024Article
- Smart Molecular Imaging and Theranostic Probes by Enzymatic Molecular In Situ Self-Assembly.JACS Au · 2024Review
- Article
- Accelerating Cellular Uptake with Unnatural Amino Acid for Inhibiting Immunosuppressive Cancer Cells.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- A continuously efficient OJournal of nanobiotechnology · 2024Article
- Enzymatic control of intermolecular interactions for generating synthetic nanoarchitectures in cellular environment.Science and technology of advanced materials · 2024Review
- Therapeutic Supramolecular Polymers: Designs and Applications.Progress in polymer science · 2024Article
- Peptide Assemblies for Cancer Therapy.ChemMedChem · 2023Review
- Evaluating Alkaline Phosphatase-Instructed Self-Assembly of d-Peptides for Selectively Inhibiting Ovarian Cancer Cells.Journal of medicinal chemistry · 2023Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Targeting organelles by modulating the redox potential of mitochondria is a promising approach to kill cancer cells that minimizes acquired drug resistance. However, it lacks selectivity because mitochondria perform essential functions for (almost) all cells. We show that enzyme-instructed self-assembly (EISA), a bioinspired molecular process, selectively generates the assemblies of redox modulators (e.g., triphenyl phosphinium (TPP)) in the pericellular space of cancer cells for uptake, which allows selectively targeting the mitochondria of cancer cells. The attachment of TPP to a pair of enantiomeric, phosphorylated tetrapeptides produces the precursors (L-1P or D-1P) that form oligomers. Upon dephosphorylation catalyzed by ectophosphatases (e.g., alkaline phosphatase (ALP)) overexpressed on cancer cells (e.g., Saos2), the oligomers self-assemble to form nanoscale assemblies only on the surface of the cancer cells. The cancer cells thus uptake these assemblies of TPP via endocytosis, mainly via a caveolae/raft-dependent pathway. Inside the cells, the assemblies of TPP-peptide conjugates escape from the lysosome, induce dysfunction of mitochondria to release cytochrome c, and result in cell death, while the controls (i.e., omitting TPP motif, inhibiting ALP, or removing phosphate trigger) hardly kill the Saos2 cells. Most importantly, the repeated stimulation of the cancers by the precursors, unexpectedly, sensitizes the cancer cells to the precursors. As the first example of the integration of subcellular targeting with cell targeting, this study validates the spatial control of the assemblies of nonspecific cytotoxic agents by EISA as a promising molecular process for selectively killing cancer cells without inducing acquired drug resistance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.