Matrix Metalloproteinase- and pH-Sensitive Nanoparticle System Enhances Drug Retention and Penetration in Glioblastoma

Pere Dosta, Michelle Z. Dion, Michaela Prado, Pau Hurtado, Cristobal J. Riojas-Javelly, Alexander M. Cryer, Yael Soria, Nelly Andrews Interiano, Gonzalo Muñoz-Taboada, Natalie Artzi

Producció científica: Article en revista indexadaArticleAvaluat per experts

5 Cites (Scopus)

Resum

Glioblastoma (GBM) is a primary malignant brain tumor with limited therapeutic options. One promising approach is local drug delivery, but the efficacy is hindered by limited diffusion and retention. To address this, we synthesized and developed a dual-sensitive nanoparticle (Dual-NP) system, formed between a dendrimer and dextran NPs, bound by a dual-sensitive [matrix metalloproteinase (MMP) and pH] linker designed to disassemble rapidly in the tumor microenvironment. The disassembly prompts the in situ formation of nanogels via a Schiff base reaction, prolonging Dual-NP retention and releasing small doxorubicin (Dox)-conjugated dendrimer NPs over time. The Dual-NPs were able to penetrate deep into 3D spheroid models and detected at the tumor site up to 6 days after a single intratumoral injection in an orthotopic mouse model of GBM. The prolonged presence of Dual-NPs in the tumor tissue resulted in a significant delay in tumor growth and an overall increase in survival compared to untreated or Dox-conjugated dendrimer NPs alone. This Dual-NP system has the potential to deliver a range of therapeutics for efficiently treating GBM and other solid tumors.

Idioma originalAnglès
Pàgines (de-a)14145-14160
Nombre de pàgines16
RevistaACS Nano
Volum18
Número22
DOIs
Estat de la publicacióPublicada - 4 de juny 2024
Publicat externament

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