Intranasal Administration of Catechol-Based Pt(IV) Coordination Polymer Nanoparticles for Glioblastoma Therapy

Abstract

Cisplatin has been described as a potent anticancer agent for decades. However, in the case of glioblastomas, it is only considered a rescue treatment applied after the failure of second-line treatments. Herein, based on the versatility offered by coordination chemistry, we engineered nanoparticles by reaction of a platinum (IV) prodrug and iron metal ions showing in vitro dual pH- and redox-sensitivity, controlled release and comparable cytotoxicity to cisplatin against HeLa and GL261 cells. In vivo intranasal administration in orthotopic preclinical GL261 glioblastoma tumor-bearing mice demonstrated increased accumulation of platinum in tumors, leading in some cases to complete cure and prolonged survival of the tested cohort. This was corroborated by a magnetic resonance imaging follow-up, thus opening new opportunities for intranasal glioblastoma therapies while minimizing side effects. The findings derived from this research showed the potentiality of this approach as a novel therapy for glioblastoma treatment.

Metallodrugs in the battle against non-small cell lung cancer: unlocking the potential for improved therapeutic outcomes

“…Nanoparticle-based delivery systems have emerged as a promising approach to improve the pharmacokinetic properties and therapeutic index of metallodrugs. For example, cisplatin-loaded nanoparticles engineered with iron metal ions have demonstrated improved anti-tumor efficacy and reduced side effects compared to free cisplatin in preclinical studies ( Mao et al, 2022 ). Similarly, ruthenium complexes encapsulated in liposomes or polymeric nanoparticles have shown enhanced tumor targeting and anti-cancer activity in vitro and in vivo ( Shen et al, 2017 ; Ma et al, 2019 ).…”

Advances in Preclinical/Clinical Glioblastoma Treatment: Can Nanoparticles Be of Help?

“…The preclinical and clinical studies using this administration route predict a breakthrough advancement in the fight against GB and have demonstrated the benefits of intranasal administration versus classical routes. In fact, our research groups have initiated this type of preclinical studies with very promising results, which encourage the developing of advanced and improved nanomedicines for GB treatment [184,185].…”

Platinum-Based Nanoformulations for Glioblastoma Treatment: The Resurgence of Platinum Drugs?

“…Specifically, for minimizing drug resistance and side effects of platinum-based anticancer drugs/prodrugs while increasing their efficacy, efficient delivery systems based on cancer-specific targeting can be used [ 88 , 89 ]. Thus, different drug delivery systems including liposomes [ 90 ], dendrimers [ 52 , 91 ], polymers [ 92 ], nanotubes [ 93 ], or inorganic [ 94 , 95 ] and hybrid [ 96 ] nanoparticles have been evaluated with these purposes. Among them, liposomes are one of the most developed and promising drug carriers for platinum-based drugs [ 97 ], showing excellent effects without toxicity in phase I clinical trials [ 98 ].…”

“…Duan et al summarized several cisplatin-based nanoformulations with potential for clinic translation [ 127 ]. Reports related to the use of NPs for brain tumour treatment date back at least 10 years, with the encapsulation of cisplatin in polymeric NPs [ 128 , 129 , 130 , 131 ], polymeric micelles [ 132 , 133 , 134 ], polymeric conjugates [ 135 , 136 ], dendrimers [ 137 , 138 ], liposomes [ 139 , 140 , 141 ], nanocapsules [ 142 , 143 ], or its integration into metallic nanoparticles [ 144 , 145 , 146 , 147 ], silica nanoparticles [ 148 , 149 , 150 ], or hybrid nanoparticles (i.e., carbon nanotubes, nanoscale coordination polymers) [ 96 , 151 , 152 , 153 , 154 , 155 , 156 , 157 , 158 ]. Most of the published examples showed improved antitumoural effects, enhanced BBB crossing, and decreased side effects in comparison with free drugs.…”

“…This nanoformulation presents dual pH and redox sensitivity in vitro, showing controlled release and comparable cytotoxicity to cisplatin against HeLa and GL261 GB cells. Interestingly, in vivo intranasal administration in orthotopic preclinical GL261 GB-bearing mice demonstrated increased accumulation of platinum in tumours, leading in certain cases to cure and prolonged survival of the tested cohort ( Figure 7 ) [ 96 ]. Additionally, the presence of magnetically active iron(III) ions allows these NPs to be proposed as potential nanoprobes to be tracked in vivo by MRI, thus opening new opportunities for the design of intranasal glioblastoma therapies while minimizing side effects.…”