Therapeutic nanosystems co-deliver anticancer drugs and oncogene SiRNA to achieve synergetic precise cancer...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Combination therapy using chemotherapeutics and small interfering RNA (siRNA) offers a promising strategy for cancer treatment.
• Glioblastoma presents a significant therapeutic challenge due to its aggressive nature and the blood-brain barrier (BBB).
• Targeted drug delivery systems are crucial for enhancing therapeutic efficacy and minimizing side effects.

Purpose of the Study:

• To design and characterize a novel cancer-targeted, pH-sensitive nanosystem for the co-delivery of doxorubicin (DOX) and c-myc siRNA against glioblastoma.
• To evaluate the stability, cellular uptake, targeting specificity, and drug release profile of the developed nanosystem.
• To assess the efficacy of the nanosystem in penetrating the blood-brain barrier and its antitumor activity in vitro and in vivo.

Main Methods:

• Fabrication of selenium nanoparticles (SeNPs) core loaded with doxorubicin (DOX).
• Decoration of SeNPs with PAMAM-RGD for cancer targeting and c-myc siRNA delivery.
• Assessment of nanosystem stability, pH-triggered drug release, cellular uptake, and targeting selectivity.
• In vitro evaluation using a blood-brain barrier model and U251 tumor spheroids.

Main Results:

• The RGD-SeNPs/siRNA nanosystem demonstrated high stability in aqueous and biological solutions.
• PAMAM-RGD decoration significantly enhanced cellular uptake and cancer cell selectivity.
• The nanosystem exhibited pH-sensitive expansion at pH 5.3, prolonging drug release and reducing side effects.
• Effective blood-brain barrier penetration and enhanced antitumor activity were observed in vitro.
• Promising penetration and inhibitory effects on U251 tumor spheroids indicate in vivo anticancer potential.

Conclusions:

• The developed cancer-targeted, pH-sensitive nanosystem (RGD-SeNPs/siRNA) is a viable platform for co-delivering chemotherapeutics and siRNA for glioblastoma treatment.
• The nanosystem effectively overcomes the blood-brain barrier and demonstrates significant antitumor potential.
• This strategy provides a foundation for designing advanced nanoplatforms for synergistic cancer therapy.