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J Control Release ; 319: 311-321, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-31911154

RESUMO

Glioblastoma multiforme (GBM) is the most common and devastating type of primary brain cancer. Despite surgery and chemo/radiation therapy, recurrence often takes place and leads to patient death. We report here on the development of a camptothecin (CPT)-based self-assembling prodrug (SAPD) hydrogel that can be used as an adjunct therapy for local treatment of GBM following maximal tumor resection. When dispersed in aqueous solution, the designed CPT prodrug spontaneously assembles into supramolecular filaments with a 100% CPT loading. In both in vitro and ex vivo assays, we show that the designed CPT prodrug can be steadily released from its supramolecular filament hydrogel, effectively killing primary GBM cells derived from patients. We also found that the solution containing self-assembling CPT filaments can be directly applied to the tumor cavity after surgical removal, and forms a gel immediately upon contact with the brain tissue. Our in vivo studies with a resection and recurrence mouse model suggest that this prodrug hydrogel can release cancer therapeutics into brain parenchyma over a long period of time, suppressing tumor recurrence and leading to prolonged survival. We believe that the simplicity in prodrug design and the high efficacy in suppressing GBM growth enable the unique potential of this SAPD hydrogels for clinical translation as an adjunct therapy for GBM treatment.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Pró-Fármacos , Animais , Neoplasias Encefálicas/tratamento farmacológico , Camptotecina , Linhagem Celular Tumoral , Glioblastoma/tratamento farmacológico , Humanos , Camundongos
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