ArticleSignal transduction and targeted therapy2024
Sequential responsive nano-PROTACs for precise intracellular delivery and enhanced degradation efficacy in colorectal cancer therapy.
Article in Signal transduction and targeted therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed.
- An oral coral-like resveratrol nanocomplex protects against dry eye disease through ocular and systemic redox homeostasis.Bioactive materials · 2027Article
- Targeted proteoform degradation for precision drug design, delivery, and therapy.Drug delivery · 2026Review
- Advancing PROTAC therapeutics through chemistry-guided design of smart delivery systems.Acta pharmacologica Sinica · 2026Review
- Nanotechnology-Enabled Targeted Protein Degradation: Strategies, Opportunities, and Challenges.Small methods · 2026Review
- Delivering Degradation: Nanomedicine and Programmable Proximity Platforms for Targeted Protein Degradation.Pharmaceutics · 2026Review
- An antibody-PROTAC conjugate targets BRD4/c-Myc/PD-L1 to enhance immunotherapy efficacy in triple-negative breast cancer.Cell reports. Medicine · 2026Article
- Autonomously Motile Nano-PROTACs Act as Protein-Sweeping Robots to Enhance Targeted Protein Degradation.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Engineering Polymeric Nano-PROTAC for Targeted Protein Degradation and Cancer Therapy.Polymer science & technology (Washington, D.C.) · 2026Review
- FDA Approval of the First-Ever PROTAC: Vepdegestrant (ARV-471) Marks a New Era in Targeted Protein Degradation.Journal of medicinal chemistry · 2026Article
- PROTAC-mediated regulation of programmed cell death: From molecular mechanisms to therapeutic breakthroughs.Innovation (Cambridge (Mass.)) · 2026Review
- Research Trends and Emerging Frontiers in Proteolysis Targeting Chimeras (PROTACs): A Bibliometric Analysis of 2630 Publications (2001-2025).Pharmaceuticals (Basel, Switzerland) · 2026Article
- pH-Responsive Materials for Therapy and Precision Biomedical Imaging.Chemical & biomedical imaging · 2026Review
- Innovative peptide-loaded hybrid membrane nanovaccine enables precise personalized immunotherapy for HPV-related cervical diseases.Signal transduction and targeted therapy · 2026Article
- Lactate metabolism-driven lactylation: paradoxical modulation of intestinal inflammation and malignancy.Journal of translational medicine · 2026Review
- The application of drug delivery systems based on targeted protein degradation chimeras in disease treatment strategies.Journal of nanobiotechnology · 2026Review
- Revolutionizing protein degradation: Harnessing nanoparticles for PROTAC delivery.Materials today. Bio · 2026Review
- Targeted Degradation of eEF2K by a Structure-Guided PROTAC Strategy for the Treatment of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nano-PROTACs for precision medicine: engineering strategies for enhanced targeting and potency.Journal of nanobiotechnology · 2026Review
- Multidimensional analysis of deubiquitinating enzymes in colorectal cancer: biological mechanisms and targeted therapeutic strategies.Frontiers in oncology · 2026Review
- Research progress and future perspectives in proteolysis-targeting chimeras.Frontiers in pharmacology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
Abstract
PROteolysis TArgeting Chimeras (PROTACs) have been considered the next blockbuster therapies. However, due to their inherent limitations, the efficacy of PROTACs is frequently impaired by limited tissue penetration and particularly insufficient cellular internalization into their action sites. Herein, based on the ultra-pH-sensitive and enzyme-sensitive nanotechnology, a type of polymer PROTAC conjugated and pH/cathepsin B sequential responsive nanoparticles (PSRNs) are deliberately designed, following the construction of the PROTAC for Cyclin-dependent kinase 4 and 6 (CDK4/6). Colorectal cancer (CRC) which hardly responds to many treatments even immune checkpoint blockades was selected as the tumor model in this study. As a result, PSRNs were found to maintain nanostructure (40 nm) in circulation and efficiently accumulated in tumors via enhanced permeation and retention effect. Then, they were dissociated into unimers (<10 nm) in response to an acidic tumor microenvironment, facilitating tumor penetration and cellular internalization. Eventually, the CDK4/6 degrading PROTACs were released intracellularly following the cleavage of cathepsin B. Importantly, PSRNs led to the enhanced degradation of target protein in vitro and in vivo. The degradation of CDK4/6 also augmented the efficacy of immune checkpoint blockades, through the upregulation of programmed cell death-ligand 1 (PD-L1) expression in cancer cells and the suppression of regulatory T cells cell proliferation in tumor microenvironment. By combination with α-PD-1, an enhanced anti-tumor outcome is well achieved in CT26 tumor model. Overall, our study verifies the significance of precise intracellular delivery of PROTACs and introduces a promising therapeutic strategy for the targeted combination treatment of CRC.
Indexed as
Identifiers
What OpenQuestion holds
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.