Recent Advances in Nanoparticle-Based Strategies for Overcoming Hypoxia in Glioblastoma Photodynamic Therapy
- 1Doctoral School, Faculty of Medicine, Collegium Medicum, University of Rzeszów, 35-310 Rzeszów, Poland
- 2Department of Photomedicine and Physical Chemistry, Faculty of Medicine, Collegium Medicum, University of Rzeszow, 35-310 Rzeszów, Poland
Abstract
Glioblastoma (GBM) remains one of the most aggressive primary brain tumours, and its hypoxic microenvironment represents a major barrier to effective photodynamic therapy (PDT). Reduced oxygen availability limits reactive oxygen species generation, while oxygen consumption during PDT may further aggravate tumour hypoxia and promote adaptive mechanisms associated with treatment resistance. A literature search covering January 2024 to August 2026 was conducted in PubMed, Scopus, and Web of Science using the Boolean query “PDT AND nanoparticles”. Original experimental studies investigating nanoparticle-based PDT in glioblastoma, with particular emphasis on strategies addressing hypoxia-related limitations, were considered eligible. Twelve studies were included in the qualitative synthesis and critically evaluated in terms of oxygen-modulating strategies, preservation of photodynamic activity under hypoxic conditions, therapeutic efficacy, and biosafety. The analysed nanoplatforms employ two principal strategies: direct alleviation of tumour hypoxia through local oxygen generation and partial circumvention of oxygen dependence through photochemical mechanisms that remain effective under reduced oxygen availability. Catalytic components including Pt, MnO2 and Fe3O4@BiFeO3 enable the conversion of endogenous H2O2 into oxygen, whereas type I photodynamic reactions provide an alternative means of maintaining ROS generation under hypoxic conditions. Beyond hypoxia modulation, multifunctional nanoplatforms integrate PDT with complementary therapeutic mechanisms, including photothermal therapy, redox disruption, ferroptosis, targeted protein degradation using PROTACs and immunomodulation. Several systems have demonstrated promising antitumour activity in experimental GBM models together with favourable preliminary biosafety profiles. However, substantial heterogeneity in experimental models, administration routes and irradiation protocols, as well as unresolved issues concerning long-term safety, blood–brain barrier penetration and clinical translation, remain important challenges. Overall, multifunctional nanoplatforms capable of modulating tumour hypoxia while simultaneously targeting additional mechanisms of GBM resistance represent a promising direction for the further development of PDT.
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BibTeX
@article{woznicki2026recent,
title = {{Recent Advances in Nanoparticle-Based Strategies for Overcoming Hypoxia in Glioblastoma Photodynamic Therapy}},
author = {Paweł Woźnicki and David Aebisher},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms272110041},
url = {https://www.mdpi.com/1422-0067/27/21/10041},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Recent Advances in Nanoparticle-Based Strategies for Overcoming Hypoxia in Glioblastoma Photodynamic Therapy
AU - Paweł Woźnicki
AU - David Aebisher
PY - 2026
DA - 2026/11/09
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms272110041
UR - https://www.mdpi.com/1422-0067/27/21/10041
AB - Glioblastoma (GBM) remains one of the most aggressive primary brain tumours, and its hypoxic microenvironment represents a major barrier to effective photodynamic therapy (PDT). Reduced oxygen availability limits reactive oxygen species generation, while oxygen consumption during PDT may further aggravate tumour hypoxia and promote adaptive mechanisms associated with treatment resistance. A literature search covering January 2024 to August 2026 was conducted in PubMed, Scopus, and Web of Science using the Boolean query “PDT AND nanoparticles”. Original experimental studies investigating nanoparticle-based PDT in glioblastoma, with particular emphasis on strategies addressing hypoxia-related limitations, were considered eligible. Twelve studies were included in the qualitative synthesis and critically evaluated in terms of oxygen-modulating strategies, preservation of photodynamic activity under hypoxic conditions, therapeutic efficacy, and biosafety. The analysed nanoplatforms employ two principal strategies: direct alleviation of tumour hypoxia through local oxygen generation and partial circumvention of oxygen dependence through photochemical mechanisms that remain effective under reduced oxygen availability. Catalytic components including Pt, MnO2 and Fe3O4@BiFeO3 enable the conversion of endogenous H2O2 into oxygen, whereas type I photodynamic reactions provide an alternative means of maintaining ROS generation under hypoxic conditions. Beyond hypoxia modulation, multifunctional nanoplatforms integrate PDT with complementary therapeutic mechanisms, including photothermal therapy, redox disruption, ferroptosis, targeted protein degradation using PROTACs and immunomodulation. Several systems have demonstrated promising antitumour activity in experimental GBM models together with favourable preliminary biosafety profiles. However, substantial heterogeneity in experimental models, administration routes and irradiation protocols, as well as unresolved issues concerning long-term safety, blood–brain barrier penetration and clinical translation, remain important challenges. Overall, multifunctional nanoplatforms capable of modulating tumour hypoxia while simultaneously targeting additional mechanisms of GBM resistance represent a promising direction for the further development of PDT.
SN - 1422-0067
ER -