Brain Co‐Delivery of Temozolomide and Cisplatin for Combinatorial Glioblastoma Chemotherapy

• Published in: Advanced materials (Weinheim) Vol. 34; no. 33; pp. e2203958 - n/a
• Main Authors: Zou, Yan, Wang, Yibin, Xu, Sen, Liu, Yanjie, Yin, Jinlong, Lovejoy, David B., Zheng, Meng, Liang, Xing‐Jie, Park, Jong Bae, Efremov, Yuri M., Ulasov, Ilya, Shi, Bingyang
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.08.2022
• Subjects: Biomimetics; Blood; blood–brain barrier; Brain; brain delivery; Cell membranes; Chemotherapy; combinational chemotherapy; Combinatorial analysis; Controlled release; Drug therapy; Effectiveness; glioblastoma; Homology; Materials science; Nanoparticles; Side effects
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202203958

Glioblastoma (GBM) is an intractable malignancy with high recurrence and mortality. Combinatorial therapy based on temozolomide (TMZ) and cisplatin (CDDP) shows promising potential for GBM therapy in clinical trials. However, significant challenges include limited blood–brain‐barrier (BBB) penetration, poor targeting of GBM tissue/cells, and systemic side effects, which hinder its efficacy in GBM therapy. To surmount these challenges, new GBM‐cell membrane camouflaged and pH‐sensitive biomimetic nanoparticles (MNPs) inspired by the fact that cancer cells readily pass the BBB and localize with homologous cells, are developed. This study's results show that MNPs can efficiently co‐load TMZ and CDDP, transport these across the BBB to specifically target GBM. Incorporation of pH‐sensitive polymer then allows for controlled release of drug cargos at GBM sites for combination drug therapy. Mice bearing orthotopic U87MG or drug‐resistant U251R GBM tumor and treated with MNPs@TMZ+CDDP show a potent anti‐GBM effect, greatly extending the survival time relative to mice receiving single‐drug loaded nanoparticles. No obvious side effects are apparent in histological analyses or blood routine studies. Considering these results, the study's new nanoparticle formulation overcomes multiple challenges currently limiting the efficacy of combined TMZ and CDDP GBM drug therapy and appears to be a promising strategy for future GBM combinatorial chemotherapy. Glioblastoma (GBM) cell membrane camouflaged biomimetic nanoparticles (MNPs) with pH‐sensitive polymer as core are developed for effective temozolomide (TMZ) and cisplatin (CDDP) brain‐targeting co‐delivery, achieving effective antitumor efficacy in both U87MG‐ and TMZ‐resistant U251R orthotopic mice models with negligible side effects.