A switch-on chemo-photothermal nanotherapy impairs glioblastoma

abstract

Judiciously combined modality approaches have proved highly effective for treating most forms of cancer, including glioblastoma. This study introduces a hybrid nanoparticle-based treatment designed to induce a synergistic effect. It employs repurposed celecoxib-loaded hybrid nanoparticles (HNPs) that are thermally activated by near-infrared laser irradiation to damage glioblastoma cells. The HNPs are constructed by covalently binding organic (ultra-small nanostructured lipid carriers, usNLCs) and inorganic nanoparticles (gold nanorods, AuNRs, with photothermal therapy capability), using c(RGDfK) that serves the dual purpose of a biolinker and a tumor-targeting peptide. The HNPs are further functionalized with transferrin (Tf) as a blood-brain barrier ligand denoted as HNPsTf. Our comprehensive in vitro and in vivo studies have unveiled the remarkable capability of HNPsTf to safely and specifically increase blood-brain barrier permeability through transferrin receptor interactions, facilitating precise nanoparticle accumulation in the tumor region within orthotopic tumor-bearing mice. Furthermore, the orchestrated combination of chemo- and photothermal therapy has exhibited a substantial therapeutic impact on glioblastoma, showcasing a noteworthy 78% inhibition in tumor volume growth and an impressive 98% delay in tumor growth. Notably, this treatment approach has resulted in prolonged survival rates among tumor-bearing mice, accompanied by a favorable side effect profile. Overall, our findings unequivocally demonstrate that celecoxib-loaded HNPsTf offer a game-changing, chemo-photothermal combination, unleashing a synergistic effect that significantly enhances both brain drug delivery and the efficacy of anti-glioblastoma treatments.

keywords

SOLID LIPID NANOPARTICLES; BLOOD-BRAIN-BARRIER; GOLD NANORODS; IN-VITRO; PHYSICOCHEMICAL PROPERTIES; SURFACE-CHEMISTRY; CELLULAR UPTAKE; THERAPY; SIZE; CYTOTOXICITY

subject category

Chemistry; Materials Science

authors

Mendes, M; António, M; Daniel-da-Silva, AL; Sereno, J; Oliveira, R; Arnaut, LG; Gomes, C; Ramos, ML; Castelo-Branco, M; Sousa, J; Pais, A; Vitorino, C

Groups

G1 - Porous Materials and Nanosystems

Projects

CICECO - Aveiro Institute of Materials (UIDB/50011/2020)

CICECO - Aveiro Institute of Materials (UIDP/50011/2020)

Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)

Collaboratory for Emerging Technologies, CoLab (EMERGING TECHNOLOGIES)

acknowledgements

Fundacao para a Ciencia e a Tecnologia (FCT) supports the Coimbra Chemistry Centre through the Project UID/QUI/00313/2020. Maria Mendes acknowledges the PhD research grant SFRH/BD/133996/2017 and COVID/BD/152172/2021 assigned by FCT. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 (DOI: https://doi.org/10.54499/UIDB/50011/2020), UIDP/50011/2020 (DOI: https://doi.org/10.54499/UIDP/50011/2020) & LA/P/0006/2020 (DOI: https://doi.org/10.54499/LA/P/0006/2020), financed by national funds through the FCT/MCTES (PIDDAC). Figures and graphical abstracts were created with https://BioRender.com. The support of Professor Ricardo Castro, and Dr Rui Manadas from UCQFarma is also acknowledged for making DSC, ATR-FTIR, and XRPD facilities available. We also acknowledge Professor Amilcar Ramalho for making the Testo 875 - Infrared camera available.