Glioblastoma is acknowledged as the most aggressive cerebral
tumor in adults. However, the efficacy of current standard
therapy is seriously undermined by drug resistance and suppressive immune microenvironment. Ferroptosis is a recently discovered form of
iron-dependent cell death that may have excellent prospect as chemosensitizer. The utilization of ferropotosis inducer
Erastin could significantly mediate
chemotherapy sensitization of
Temozolomide and exert anti-
tumor effects in
glioblastoma. In this study, a combination of
hydrogel-
liposome nanoplatform encapsulated with
Temozolomide and ferroptosis inducer
Erastin was constructed. The αvβ3
integrin-binding
peptide cyclic RGD was utilized to modify codelivery system to achieve
glioblastoma targeting strategy. As biocompatible drug reservoirs, cross-linked GelMA (
gelatin methacrylamide)
hydrogel and cRGD-coated
liposome realized the sustained release of internal contents. In the modified intracranial
tumor resection model, GelMA-
liposome system achieved slow release of
Temozolomide and
Erastin in situ for more than 14 d. The results indicated that nanoplatform (T+E@LPs-cRGD+GelMA) improved
glioblastoma sensitivity to chemotherapeutic
temozolomide and exerted satisfactory anti-
tumor effects. It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance. Furthermore, transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform (T+E@LPs-cRGD+GelMA) implicated in. It is suggested that GelMA-
liposome system participated in the immune response and
immunomodulation of
glioblastoma via
interferon/PD-L1 pathway. Collectively, this study proposed a potential combinatory therapeutic strategy for
glioblastoma treatment.