High‐Load CoreShell Nanocarriers with Irinotecan and 5‐Fluorouracil for Combination Chemotherapy in Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer type and second leading cause of cancer‐related deaths worldwide, requiring novel drug‐delivery concepts. ITC@ZrO (TocP)/ZrO (FdUMP) core@shell nanocarriers (designated ITC‐FdUMP‐NC) with the clinically relevant chemotherapeutics irinotecan (ITC) and fluoro‐2′‐deoxyuridine‐5′‐phosphate (FdUMP) (active derivative of 5′‐fluorouracil/5‐FU) are a new type of nanocarrier with high drug payload (22 wt% of lipophilic ITC: particle core; 10 wt% of hydrophilic FdUMP: particle shell). The nanocarriers are tested in different CRC cell lines, a normal cell line, and rectal cancer patient‐derived organoids (PDOs). Fluorescence‐labeled nanocarriers show efficient uptake by all CRC cells and allow to distinctly track the intracellular trafficking toward endolysosomal compartments. Although free chemotherapeutic drugs exhibit a greater potency in 2D cell cultures, ITC‐FdUMP‐NC demonstrate equivalent cytotoxic efficacies as the freely dissolved drugs in the more complex 3D rectal cancer PDOs. The sustained drug‐release profile of the nanocarriers contrasts favorably with conventional free drugs, potentially enhancing the therapeutic outcome in vivo. With a chemotherapeutic cocktail comparable to the clinically applied FOLFIRI (ITC + 5‐FU), the ITC‐FdUMP‐NC represent a novel type of nanocarrier with high anti‐tumor effect and high drug payload, offering a promising strategy to circumvent chemoresistance and to improve therapy efficacy in vivo with less side effects.

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch

Erschienen in
High‐Load CoreShell Nanocarriers with Irinotecan and 5‐Fluorouracil for Combination Chemotherapy in Colorectal Cancer ; day:19 ; month:08 ; year:2024 ; extent:14
Small science ; (19.08.2024) (gesamt 14)

Urheber
Notter, Silke
Choezom, Dolma
Griebel, Titus
Ramos‐Gomes, Fernanda
Möbius, Wiebke
De Oliveira, Tiago
Conradi, Lena‐Christin
Alves, Frauke
Feldmann, Claus

DOI
10.1002/smsc.202400196
URN
urn:nbn:de:101:1-2408201431205.832417907737
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
14.08.2025, 10:46 MESZ

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Beteiligte

  • Notter, Silke
  • Choezom, Dolma
  • Griebel, Titus
  • Ramos‐Gomes, Fernanda
  • Möbius, Wiebke
  • De Oliveira, Tiago
  • Conradi, Lena‐Christin
  • Alves, Frauke
  • Feldmann, Claus

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