Homotype-Targeted Biogenic Nanoparticles to Kill Multidrug-Resistant Cancer Cells

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Nanoparticle drug delivery faces challenges with off-targeting and low receptor density, limiting efficacy.
• Multidrug resistance (MDR) in cancer cells significantly compromises treatment outcomes.

Purpose of the Study:

• To develop cell membrane-cloaked biogenic nanoparticles for co-delivery of paclitaxel (PTX) and disulfiram (DSF).
• To enhance nanoparticle targeting and drug delivery specifically to MDR cancer cells via homotypic binding.

Main Methods:

• Isolation of cancer cell membranes (A549/T) for coating hybrid nanoparticles.
• Construction of A549/T cell membrane-hybrid nanoparticles (A549/T CM-HNPs).
• Evaluation of nanoparticle uptake, P-glycoprotein (P-gp) inhibition, and apoptosis induction in MDR cells.

Main Results:

• A549/T CM-HNPs demonstrated selective recognition and a ninefold increase in uptake in homologous MDR cells through homotypic binding.
• The nanoparticles suppressed P-gp activity by 3.2-fold, sensitizing MDR cells to paclitaxel.
• Effective apoptosis induction (70%) was observed in homologous A549/T cells.

Conclusions:

• Cell membrane coating utilizing "homotypic binding" is a promising strategy for targeted drug delivery to MDR cancer cells.
• This approach enhances chemotherapeutic accumulation and improves therapeutic outcomes in MDR cancers.
• A549/T CM-HNPs show potential for overcoming multidrug resistance and improving cancer treatment efficacy.