An oral delivery approach for riboflavin-targeted platinum(II)-loaded lipid nanoparticles into alginate-gelatin matrices against 2D and 3D colorectal carcinoma models

被引：0

作者：

Boztepe, Tugce ^{[1
]}

Karp, Federico ^{[1
]}

Cabrera, Silvia ^{[2
]}

Aleman, Jose ^{[3
]}

Lamas, Diego G. ^{[4
]}

Huck-Iriart, Cristian ^{[4
,5
]}

Islan, German A. ^{[1
,6
]}

Leon, Ignacio E. ^{[7
,8
]}

机构：

[1] CONICET UNLP CCT La Plata, Fac Ciencias Exactas, Ctr Invest & Desarrollo Fermentac Ind CINDEFI, Lab Nanobiomat,Dept Quim, La Plata, Buenos Aires, Argentina

[2] Univ Autonoma Madrid, Dept Quim Inorgan, Madrid 28049, Spain

[3] Univ Autonoma Madrid, Dept Quim Organ, Madrid 28049, Spain

[4] UNSAM CONICET, Escuela Ciencia & Tecnol ECyT, Lab Cristalog Aplicada LCA, Inst Tecnol Emergentes & Ciencias Aplicadas ITECA, Campus Miguelete, RA-1650 San Martin, Buenos Aires, Argentina

[5] ALBA Synchrotron Light Source, Carrer Llum 2-26, Barcelona 08290, Spain

[6] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Childrens Hosp, Langenbeckstr 1, D-55131 Mainz, Germany

[7] Univ Nacl La Plata, Fac Ciencias Exactas, CEQUINOR UNLP, CCT CONICET La Plata,Dept Quim,CIC, Blvd 120 N 1465, RA-1900 La Plata, Argentina

[8] Univ Nacl La Plata, Fac Ciencias Exactas, Dept Ciencias Biol, Catedra Fisiopatol, 47 & 115, RA-1900 La Plata, Argentina

来源：

JOURNAL OF INORGANIC BIOCHEMISTRY | 2025年 / 269卷

关键词：

Drug delivery; Colorectal cancer; Platinum; Riboflavin; Alginate; Gelatin; CARRIER PROTEIN; COMPLEXES; OXALIPLATIN; CANCER; 8-HYDROXYQUINOLINE; PROLIFERATION; DECOMPOSITION; CYTOTOXICITY; SUBSTITUTION; CARBOPLATIN;

D O I：

10.1016/j.jinorgbio.2025.112900

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

This study investigated the use of riboflavin-targeted Nanostructured Lipid Carriers (R-NLCs) to deliver a platinum-based anticancer drug [PtCl(8-O-quinolinate)(dmso)] (8-QO-Pt) to colorectal cancer cells. Three different R-8-QO-Pt-NLC formulations were prepared via hot-homogenization by ultrasonication method. The physicochemical characterizations of NLCs were analyzed by small-and wide-angle X-ray scattering (SAXS/ WAXS) and fourier transformed infrared spectroscopy (FTIR). The cytotoxic effects and IC50 values of R-8-QO-PtNLC formulations were compared with those of the free 8-QO-Pt. Cellular uptake and apoptosis were evaluated towards HCT 116 cells in monolayer (2D). The liquid overlay technique was used to generate 3D multicellular tumor spheroids, MCTS. The anticancer and antimetastatic activities of the free 8-QO-Pt and R-8-QO-Pt-NLCs were determined in MCTS. The results revealed that R-8-QO-Pt-NLC exhibited greater cytotoxicity and lower IC50 values than free 8-QO-Pt in both 2D and 3D cell cultures. Furthermore, results showed that the volumes of the spheroids were reduced in response to increasing concentrations of R-8-QO-Pt-NLC, showing higher inhibition of cell migration in colorectal cancer spheroids at concentrations of 10.0, 15.0, and 25.0 mu M than free 8-QO-Pt. To provide protection against gastric acid conditions, an additional drug delivery system based on alginate (Alg) and gelatin (Gel) beads for R-8-QO-Pt-NLC oral administration was developed. While free and R-NLC encapsulated 8QO-Pt were practically inactivated at pH 1.2 and 37 degrees C, it was revealed that the Alg-Gel beads retain 5.7 times the initial activity of the R-8-QO-Pt-NLC. The findings of this research indicate that R-8-QO-Pt-NLC embedded in Alg-Gel beads are promising hydrogels for targeted colorectal delivery systems.

引用

页数：13