A Programmed Cell-Mimicking Nanoparticle Driven by Potato Alkaloid for Targeted Cancer Chemoimmunotherapy

Area of Science:

• Biomaterials Science
• Nanotechnology
• Drug Delivery Systems

Background:

• Membrane camouflaged-nanoparticles (CM-NPs) offer cell-like functionalities but their intact coating can impede drug release at tumor sites.
• Optimization of CM-NPs is crucial for improving drug delivery efficiency in tumor-targeted therapy.

Purpose of the Study:

• To design a novel cell-mimicking core-shell nanoparticle with acid-responsive off-coating properties for enhanced tumor-targeted therapy.
• To leverage Solamargine (SM) as a core component and red blood cell membrane (RBCm) for nanoparticle construction.
• To investigate the synergistic effects of the developed nanoparticle with immunotherapy.

Main Methods:

• Development of a core-shell nanoparticle (RBC-SLip) using Solamargine as the inner core and red blood cell membrane as the outer coating.
• Evaluation of acid-responsive off-coating behavior in the tumor microenvironment (TME).
• Assessment of active tumor-targeting, endosomal escape, and antitumor efficacy of the off-coating liposome (SLip).
• Investigation of chemoimmunotherapy by encapsulating paclitaxel (PTX) and combining with PD1/PD-L1 blockade.

Main Results:

• The RBC-SLip exhibits stable circulation under physiological conditions and undergoes morphological changes in acidic TME.
• The resulting SLip demonstrates enhanced active tumor-targeting and endosomal escape abilities.
• The RBC-SLip, loaded with PTX, synergizes with PD1/PD-L1 blockade, achieving superior chemoimmunotherapy and antitumor efficacy.
• Solamargine's inherent TME-modulating properties contribute to the observed synergistic effects.

Conclusions:

• The acid-responsive off-coating strategy using natural product Solamargine offers a new approach to optimize CM-NPs for tumor-targeted therapy.
• The developed RBC-SLip system enhances drug delivery and therapeutic outcomes by overcoming the limitations of intact membrane coatings.
• This approach highlights the potential of natural products in designing advanced drug delivery systems and their application in combined cancer therapies.