Small molecule based EGFR targeting of biodegradable nanoparticles containing temozolomide and Cy5 dye for greatly enhanced image-guided glioblastoma therapy

Current glioblastoma multiforme (GBM) treatment is insufficient, facing obstacles like poor tumor accumulation and dose limiting side effects of chemotherapeutic agents. Targeted nanomaterials offer breakthrough potential in GBM treatment; however, traditional antibody based targeting poses challenges for live brain application. To overcome current obstacles, we introduce here the development of a small molecule targeting agent, CFMQ, coupled to biocompatible chitosan coated poly(lactic-co-glycolic) acid nanoparticles. These targeted nanoparticles enhance cellular uptake and show rapid blood-brain barrier (BBB) permeability in-vitro, demonstrating the ability to effectively deliver their load to tumor cells. Encapsulation of the chemotherapeutic agent, temozolomide (TMZ), decreases the IC50 ~34-fold compared to free-drug. Also, CFMQ synergistically suppresses tumor cell progression, reducing colony formation (98%), cell migration (84%), and cell invasion (77%). Co-encapsulation of Cy5 enables optical image guided therapy. This biocompatible theranostic nanoformulation shows early promise in significantly enhancing the efficacy of TMZ, while providing potential for image-guided therapy for GBM. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

The development of a small molecule targeting agent CFMQ coupled with nanoparticles has shown promise in enhancing cellular uptake and blood-brain barrier permeability. Encapsulation of the chemotherapy drug TMZ in these nanoparticles significantly reduces its IC50 value and CFMQ also synergistically suppresses tumor cell progression. The co-encapsulation of Cy5 enables optical image guided therapy.