Combating multidrug resistance of breast cancer with ginsenoside Rh2-irrigated nano-in-thermogel.
Int J Pharm
; 650: 123718, 2024 Jan 25.
Article
em En
| MEDLINE
| ID: mdl-38104849
ABSTRACT
The emergence of multidrug resistance (MDR) is the leading cause of mortality in patients with breast cancer. Overexpressed P-glycoprotein (P-gp) that can pump out chemotherapeutics from multidrug-resistant cancer cells is the main cause of chemotherapy failure. P-gp inhibitors are hence increasingly used to sensitize chemotherapy to breast cancer with MDR by reducing the efflux of drugs. However, representative P-gp inhibitors usually have severe side effects and the effect of their release behavior on chemotherapy are neglected in current studies. We constructed a nano-in-thermogel delivery system with the sequential release of ginsenoside Rh2 (GRh2) and a chemotherapeutic drug in the tumor microenvironment as a drug compounding "reservoir" to combat MDR in breast cancer. Briefly, paclitaxel (PTX) and GRh2 were encapsulated in solid lipid nanoparticles (SLNs) and dispersed in a poloxamer-based thermogel (SLNs-Gel). GRh2 was used as an innovative and safe P-gp inhibitor to lower P-gp expression and cellular adenosine triphosphate context, thereby sensitizing PTX-resistant breast cancer cells (MCF-7/PTX) to PTX. Pharmacodynamic and in vivo safety studies confirmed that intratumoral injection of SLNs-Gel significantly suppressed the proliferation of PTX-resistant breast cancer and alleviated the PTX-induced hematotoxicity. The GRh2-irrigated nano-in-thermogel delivery system shows great potential in combating multidrug-resistant cancer.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Nanopartículas
Limite:
Female
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article