An all-in-one nanoparticle for overcoming drug resistance: doxorubicin and elacridar co-loaded folate receptor targeted PLGA/MSN hybrid nanoparticles

• Published in: Journal of drug targeting 2024-11, Vol.32 (9), p.1101-1110
• Main Authors: Tonbul, Hayrettin, Şahin, Adem, Öztürk, Süleyman Can, Ultav, Gözde, Tavukçuoğlu, Ece, Akbaş, Sedenay, Aktaş, Yeşim, Esendağlı, Güneş, Çapan, Yılmaz
• Format: Article
• Language: English
• Subjects: Acridines - administration & dosage; Acridines - chemistry; Acridines - pharmacology; Animals; Antibiotics, Antineoplastic - administration & dosage; Antibiotics, Antineoplastic - pharmacokinetics; Antibiotics, Antineoplastic - pharmacology; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Doxorubicin - administration & dosage; Doxorubicin - pharmacokinetics; Doxorubicin - pharmacology; Drug Carriers - chemistry; Drug Resistance, Multiple - drug effects; Drug Resistance, Neoplasm - drug effects; Female; Folic Acid - chemistry; Folic Acid Transporters - metabolism; Humans; Lactic Acid - chemistry; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles - chemistry; Polyglycolic Acid - chemistry; Polylactic Acid-Polyglycolic Acid Copolymer - chemistry; Silicon Dioxide - chemistry; Tetrahydroisoquinolines - administration & dosage; Tetrahydroisoquinolines - pharmacokinetics; Tetrahydroisoquinolines - pharmacology
• ISSN: 1061-186X; 1029-2330; 1029-2330
• DOI: 10.1080/1061186X.2024.2374034

Overexpression of permeability-glycoprotein (P-gp) transporter leads to multidrug resistance (MDR) through cellular exclusion of chemotherapeutics. Co-administration of P-gp inhibitors and chemotherapeutics is a promising approach for improving the efficacy of therapy. Nevertheless, problems in pharmacokinetics, toxicity and solubility limit the application of P-gp inhibitors. Herein, we developed a novel all-in-one hybrid nanoparticle system to overcome MDR in doxorubicin (DOX)-resistant breast cancer. First, folic acid-modified DOX-loaded mesoporous silica nanoparticles (MSNs) were prepared and then loaded into PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles along with a P-gp inhibitor, elacridar. This hybrid nanoparticle system had high drug loading capacity, enabled both passive and active targeting of tumour tissues, and exhibited sequential and pH-triggered release of drugs. and studies in DOX-resistant breast cancer demonstrated the ability of the hybrid nanoparticles to reverse P-gp-mediated drug resistance. The nanoparticles were efficiently taken up by the breast cancer cells and delivered elacridar, . Biodistribution studies demonstrated substantial accumulation of the folate receptor-targeted PLGA/MSN hybrid nanoparticles in tumour-bearing mice. Moreover, deceleration of the tumour growth was remarkable in the animals administered with the DOX and elacridar co-loaded hybrid nanoparticles when compared to those treated with the marketed liposomal DOX (Caelyx ) or its combination with elacridar.