ArticleJournal of the American Chemical Society2015
Enhancing Accumulation and Penetration of HPMA Copolymer-Doxorubicin Conjugates in 2D and 3D Prostate Cancer Cells via iRGD Conjugation with an MMP-2 Cleavable Spacer.
Article in Journal of the American Chemical Society, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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.
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Who cites it
44 citing papers in PubMed.
- Immunomodulatory Natural Products in Cancer Organoid-Immune Co-Cultures: Bridging the Research Gap for Precision Immunotherapy.International journal of molecular sciences · 2025Review
- HPMA Copolymers: A Versatile Platform for Targeted Peptide Drug Delivery.Biomolecules · 2025Review
- Doxorubicin-Conjugated Nanoparticles for Potential Use as Drug Delivery Systems.Nanomaterials (Basel, Switzerland) · 2025Review
- Hydrophilic biomaterials: From crosslinked and self-assembled hydrogels to polymer-drug conjugates and drug-free macromolecular therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Polymeric Nanoparticles for Drug Delivery.Chemical reviews · 2024Review
- Chemo-immunotherapy by dual-enzyme responsive peptide self-assembling abolish melanoma.Bioactive materials · 2024Article
- Nanodelivery systems: An efficient and target-specific approach for drug-resistant cancers.Cancer medicine · 2023Review
- Drug Delivery Strategies for the Treatment of Pancreatic Cancer.Pharmaceutics · 2023Review
- Constructed Tumor-Targeted and MMP-2 Biocleavable Antibody Conjugated Silica Nanoparticles for Efficient Cancer Therapy.ACS omega · 2023Article
- Targeting LncRNAOncology research · 2023Article
- Exosomal targeting and its potential clinical application.Drug delivery and translational research · 2022Review
- Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model.Pharmaceutics · 2022Article
- Nanomedicine Penetration to Tumor: Challenges, and Advanced Strategies to Tackle This Issue.Cancers · 2022Review
- The Impact of Tyrosine Iodination on the Aggregation and Cleavage Kinetics of MMP-9-Responsive Peptide Sequences.ACS biomaterials science & engineering · 2022Article
- Cell-Penetrating Peptides.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Nanomedicines in B cell-targeting therapies.Acta biomaterialia · 2022Review
- Delivery of Various Cargos into Cancer Cells and Tissues via Cell-Penetrating Peptides: A Review of the Last Decade.Pharmaceutics · 2021Review
- Review
- Recent advances in drug delivery systems for enhancing drug penetration into tumors.Drug delivery · 2020Review
- Engineering Prodrug Nanomedicine for Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2020Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
To enhance the accumulation and penetration of nanomedicines in tumor tissue, we developed and evaluated the biological properties of matrix metalloproteinase 2 (MMP-2)-responsive N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer drugs and tumor-penetrating peptide conjugates (P-DOX-PLGLAG-iRGD). Two different spacers were used in the design: a lysosomally (cathepsin B) cleavable tetrapeptide GFLG spacer conjugated doxorubicin (DOX) to HPMA copolymer, and an MMP-2-degradable linker (PLGLAG) connected tumor-homing and -penetrating cyclic peptide iRGD to HPMA copolymer. The accumulation of DOX in P-DOX-PLGLAG-iRGD-treated monolayer (2D) and multilayer (3D) DU-145 prostate cancer cells was higher than that of control groups (P-DOX and P-DOX + iRGD). The cell cycle arrest analysis and cytotoxicity data demonstrated that P-DOX-PLGLAG-iRGD produced a higher G2/M arrest and possessed stronger cytotoxicity against DU-145 cells than P-DOX + iRGD or P-DOX, which was consistent with the drug uptake results. Similarly, P-DOX-PLGLAG-iRGD demonstrated the highest penetration ability in 3D multicellular DU-145 tumor cell spheroids. The results indicate that covalent conjugation of iRGD via MMP-2-sensitive bonds enhances accumulation and penetration of nanomedicines into tumor cell monolayers and spheroids.
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