ArticleProceedings of the National Academy of Sciences of the United States of America2014
Detouring of cisplatin to access mitochondrial genome for overcoming resistance.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
87 citing papers in PubMed, 245 citations in OpenAlex.
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- A Mitochondria-Targeted Biomimetic Nanomedicine Capable of Reversing Drug Resistance in Colorectal Cancer Through Mitochondrial Dysfunction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Nanoparticles for Photodynamic Therapy of Breast Cancer: A Review of Recent Studies.Molecules (Basel, Switzerland) · 2025Review
- Carrier-Free Cisplatin-Dactolisib Nanoparticles for Enhanced Synergistic Antitumor Efficacy.ACS biomaterials science & engineering · 2025Article
- Recent advances in nanomedicine design strategies for targeting subcellular structures.iScience · 2025Review
- Key Nano-Strategies for Cisplatin Resistance in Advancing Anti-Cancer Therapy.International journal of nanomedicine · 2025Review
- Bifunctional Oxaliplatin (IV) Prodrug Based pH-Sensitive PEGylated Liposomes for Synergistic Anticancer Action Against Triple Negative Breast cancer.AAPS PharmSciTech · 2024Article
- Targeting mitochondria: a novel approach for treating platinum-resistant ovarian cancer.Journal of translational medicine · 2024Review
- Smart Molecular Imaging and Theranostic Probes by Enzymatic Molecular In Situ Self-Assembly.JACS Au · 2024Review
- Simultaneous targeting of peripheral and brain tumors with a therapeutic nanoparticle to disrupt metabolic adaptability at both sites.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Our current understanding of the biological impact of endometrial cancer mtDNA genome mutations and their potential use as a biomarker.Frontiers in oncology · 2024Review
- Cisplatin-based Liposomal Nanocarriers for Drug Delivery in Lung Cancer Therapy: Recent Progress and Future Outlooks.Current pharmaceutical design · 2024Review
- New Pathway for Cisplatin Prodrug to Utilize Metabolic Substrate Preference to Overcome Cancer Intrinsic Resistance.ACS central science · 2023Article
- All-in-One Pyruvate Dehydrogenase Kinase Inhibitor for Tracking, Targeting, and Enhanced Efficacy.Bioconjugate chemistry · 2023Article
- Platinum-Based Nanoformulations for Glioblastoma Treatment: The Resurgence of Platinum Drugs?Nanomaterials (Basel, Switzerland) · 2023Review
- Mitochondria as a target of third row transition metal-based anticancer complexes.Current opinion in chemical biology · 2023Review
- Application Prospects of Triphenylphosphine-Based Mitochondria-Targeted Cancer Therapy.Cancers · 2023Review
- Highlights of New Strategies to Increase the Efficacy of Transition Metal Complexes for Cancer Treatments.Molecules (Basel, Switzerland) · 2022Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Chemoresistance of cisplatin therapy is related to extensive repair of cisplatin-modified DNA in the nucleus by the nucleotide excision repair (NER). Delivering cisplatin to the mitochondria to attack mitochondrial genome lacking NER machinery can lead to a rationally designed therapy for metastatic, chemoresistant cancers and might overcome the problems associated with conventional cisplatin treatment. An engineered hydrophobic mitochondria-targeted cisplatin prodrug, Platin-M, was constructed using a strain-promoted alkyne-azide cycloaddition chemistry. Efficient delivery of Platin-M using a biocompatible polymeric nanoparticle (NP) based on biodegradable poly(lactic-co-glycolic acid)-block-polyethyleneglycol functionalized with a terminal triphenylphosphonium cation, which has remarkable activity to target mitochondria of cells, resulted in controlled release of cisplatin from Platin-M locally inside the mitochondrial matrix to attack mtDNA and exhibited otherwise-resistant advanced cancer sensitive to cisplatin-based chemotherapy. Identification of an optimized targeted-NP formulation with brain-penetrating properties allowed for delivery of Platin-M inside the mitochondria of neuroblastoma cells resulting in ∼17 times more activity than cisplatin. The remarkable activity of Platin-M and its targeted-NP in cisplatin-resistant cells was correlated with the hyperpolarization of mitochondria in these cells and mitochondrial bioenergetics studies in the resistance cells further supported this hypothesis. This unique dual-targeting approach to controlled mitochondrial delivery of cisplatin in the form of a prodrug to attack the mitochondrial genome lacking NER machinery and in vivo distribution of the delivery vehicle in the brain suggested previously undescribed routes for cisplatin-based therapy.
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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.