Stapled Acid-Sensitive Endosome Disrupting Alginates
Alginoketal nanoparticles are engineered by crosslinking alginic acid with acid-sensitive ketals that hydrolyze in low pH environments, such as endosomes. This approach enables targeted release of divalent cations, including copper, calcium, iron, and zinc, directly into the cellular cytosol. The synthesis involves forming alginoketals with bis-amino ketals and subsequent particle formation via an inverse emulsion system. Surface modifications allow these nanoparticles to adhere to negatively charged cell membranes and biofilms, while controlled degradation in acidic conditions disrupts endosomal barriers, thereby facilitating efficient cargo delivery.
Description
This technology distinguishes itself by combining a simple, natural polymer-based synthesis with highly selective, pH-responsive release mechanisms that overcome common cytotoxicity issues in drug delivery. Its ability to simultaneously encapsulate diverse therapeutic agents—ranging from immunotherapeutics to cancer cytotoxic compounds—and mimic superoxide dismutase activity when complexed with copper, offers significant advantages. Preclinical studies have demonstrated selective cancer cell death and effective biofilm targeting, positioning this system as a promising advancement in targeted treatment strategies.Applications
- Targeted cancer drug delivery- Biofilm elimination therapy
- Immunotherapy delivery system
- Neurological disorder treatment
Advantages
- Enables targeted delivery by binding selectively to negatively charged cell surfaces and biofilms.- Offers pH-sensitive degradation that triggers cargo release specifically within acidic endosomal environments.
- Provides versatile delivery of multiple divalent cations and therapeutic agents, including proteins and anti-cancer drugs.
- Minimizes cytotoxicity by avoiding harmful off-target effects and preserving healthy cells.
- Facilitates endosomal escape to ensure efficient delivery of cargo into the cellular cytosol.
- Exhibits superoxide dismutase-like activity when complexed with copper(II), contributing to selective cancer cell death.