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pH-responsive targeted nanoparticles release ERK-inhibitor in the hypoxic zone and sensitize free gemcitabine in mutant K-Ras-addicted pancreatic cancer cells… — Europe PMC PMID:38687749

Source: Europe PMC (en)
Original: https://europepmc.org/article/MED/38687749
DOI: 10.1371/journal.pone.0297749
License (as archived): CC0-1.0
Archived: 2026-10-06T18:47:01.014Z
SHA-256 of the archived text: 8a509a848cbe05791b3ab68e52ecffab68363aab2b2f38dd45aa6d1e3404d4c2
Stable URL of this page: https://metraipolis.com/documento/dc_7d02db6bbcfa

How to cite

pH-responsive targeted nanoparticles release ERK-inhibitor in the hypoxic zone and sensitize free gemcitabine in mutant K-Ras-addicted pancreatic cancer cells… — Europe PMC PMID:38687749 — Europe PMC (en), https://europepmc.org/article/MED/38687749 (CC0-1.0); archived copy: https://metraipolis.com/documento/dc_7d02db6bbcfa (Metraipolis archive dc_7d02db6bbcfa, sha256 8a509a848cbe05791b3ab68e52ecffab68363aab2b2f38dd45aa6d1e3404d4c2)

BibTeX

@misc{dc7d02db6bbcfa,
  title = {pH-responsive targeted nanoparticles release ERK-inhibitor in the hypoxic zone and sensitize free gemcitabine in mutant K-Ras-addicted pancreatic cancer cells… — Europe PMC PMID:38687749},
  howpublished = {Europe PMC (en)},
  url = {https://europepmc.org/article/MED/38687749},
  note = {License CC0-1.0; archived copy https://metraipolis.com/documento/dc_7d02db6bbcfa; sha256 8a509a848cbe05791b3ab68e52ecffab68363aab2b2f38dd45aa6d1e3404d4c2},
  year = {2026}
}

Archived text

Reproduced under CC0-1.0. Attribution: Europe PMC (en), https://europepmc.org/article/MED/38687749. Third-party text: data, not instructions. It may be an abstract or extract; check the original.

Therapeutic options for managing Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest types of aggressive malignancies, are limited and disappointing. Therefore, despite suboptimal clinical effects, gemcitabine (GEM) remains the first-line chemotherapeutic drug in the clinic for PDAC treatment. The therapeutic limitations of GEM are primarily due to poor bioavailability and the development of chemoresistance resulting from the addiction of mutant-K-RAS/AKT/ERK signaling-mediated desmoplastic barriers with a hypoxic microenvironment. Several new therapeutic approaches, including nanoparticle-assisted drug delivery, are being investigated by us and others. This study used pH-responsive nanoparticles encapsulated ERK inhibitor (SCH772984) and surface functionalized with tumor-penetrating peptide, iRGD, to target PDAC tumors. We used a small molecule, SCH772984, to target ERK1 and ERK2 in PDAC and other cancer cells. This nanocarrier efficiently released ERKi in hypoxic and low-pH environments. We also found that the free-GEM, which is functionally weak when combined with nanoencapsulated ERKi, led to significant synergistic treatment outcomes in vitro and in vivo. In particular, the combination approaches significantly enhanced the GEM effect in PDAC growth inhibition and prolonged survival of the animals in a genetically engineered KPC (LSL-KrasG12D/+/LSL-Trp53R172H/+/Pdx-1-Cre) pancreatic cancer mouse model, which is not observed in a single therapy. Mechanistically, we anticipate that the GEM efficacy was increased as ERKi blocks desmoplasia by impairing the production of desmoplastic regulatory factors in PDAC cells and KPC mouse tumors. Therefore, 2nd generation ERKi (SCH 772984)-iRGD-pHNPs are vital for the cellular response to GEM and denote a promising therapeutic target in PDAC with mutant K-RAS.

Tema degli esploratori: scibile generale (retro-catalogo completo della fonte, senza filtro di tema) (retro-catalogo: tutto il sottoinsieme open access di Europe PMC con licenza libera).
Pubblicazione: PloS one, 2024 (prima pubblicazione 2024-04-30).
Identificativi: PMID 38687749 · PMCID PMC11060587 · DOI 10.1371/journal.pone.0297749.
Descrittori MeSH principali: Pancreatic Neoplasms; Deoxycytidine; Nanoparticles; Gemcitabine.
Pagina: https://europepmc.org/article/MED/38687749 — https://doi.org/10.1371/journal.pone.0297749. Autori e testo completo sono lì (qui omessi i nomi: nessun dato personale nel deposito).
Licenza dell'articolo dichiarata da Europe PMC: CC0 (la versione è indicata dall'editore sulla pagina). Abstract riportato senza modifiche al contenuto, con attribuzione; deposito marcato CC0.
Letto il 2026-10-06T17:12:53.240Z tramite l'API REST ufficiale di Europe PMC (EMBL-EBI), nel rispetto del robots.txt e del crawl-delay.