All-in-one nanosponge with pluronic shell for synergistic anticancer therapy through effectively overcoming multidrug...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Multidrug resistance (MDR) in cancer, often mediated by P-glycoprotein (P-gp) overexpression, significantly limits chemotherapy effectiveness.
• Targeted delivery of multiple chemotherapeutic agents and P-gp inhibitors presents a promising strategy to overcome MDR in colorectal cancer.

Purpose of the Study:

• To develop and evaluate an all-in-one nanosponge (ANS) for the co-delivery of doxorubicin (DOX), paclitaxel (PTX), and the P-gp inhibitor tetrandrine (TET) to combat MDR colorectal cancer.
• To investigate the drug release profiles, in vitro and in vivo anticancer efficacy, and toxicity of the developed nanosponge formulation.

Main Methods:

• Fabrication of an all-in-one nanosponge (ANS) encapsulating DOX, PTX, and TET without chemical conjugation.
• Characterization of ANS for loading capacity, efficiency, and pH-dependent controlled release kinetics.
• In vitro evaluation of anticancer effects on P-gp-overexpressing colorectal cancer cells and in vivo assessment using solid tumor mouse xenografts.

Main Results:

• The developed DOX/PTX/TET@ANS exhibited high loading content and efficiency with distinct pH-dependent release profiles.
• DOX/PTX/TET@ANS demonstrated superior anticancer efficacy compared to free drugs and dual-drug loaded ANS against MDR colorectal cancer cells and tumors.
• The nanosponge formulation showed reduced toxicity and suggested a synergistic effect, with the pluronic shell potentially contributing to P-gp inhibition.

Conclusions:

• The all-in-one nanosponge system is a viable platform for co-delivering multiple drugs and a P-gp inhibitor to effectively treat multidrug-resistant colorectal cancer.
• This nanosponge approach offers a promising strategy to enhance chemotherapy outcomes in MDR tumors by overcoming P-gp-mediated resistance.
• The findings highlight the potential of nanocarriers for synergistic drug delivery in overcoming complex challenges in cancer therapy.