Preparation and physicochemical properties of mitochondria-targeted starch nanoparticles

Mitochondria serve as critical subcellular targets for therapeutic interventions; however, achieving precise mitochondrial targeting using biocompatible and biodegradable carriers remains challenging. Starch, which is biodegradable, biocompatible, and structurally modifiable, remains unexplored for mitochondrial targeting applications. The study aimed to synthesize (5-carboxypentyl) triphenyl phosphonium bromide (CTPP)-modified starch and fabricate starch-based nanoparticles (TMSNP) via ultrasonic anti-solvent precipitation, followed by investigation of their physicochemical properties, structural characteristics, and targeting performance. Successful conjugation of CTPP onto the starch backbone was confirmed using FT-IR and ¹H NMR spectroscopy. The TMSNP exhibited a spherical morphology, with particle sizes ranging from 150 to 200 nm and low polydispersity indices (PDI ≤ 0.3). Zeta potential analysis revealed that the potential of the nanoparticles shifted from negative to positive after CTPP modification, further confirming the successful synthesis of the TMSNP. The introduction of CTPP disrupted the native crystalline structure of starch and reduced its thermal stability. Notably, all nanoparticles demonstrated excellent biocompatibility in RAW 264.7 cells. Compared to the starch nanoparticles without CTPP modification, TMSNP demonstrated enhanced lysosomal escape and superior mitochondrial targeting ability. Furthermore, the TMSNP exhibited pronounced pH-responsive behavior. Collectively, the findings indicated that TMSNP are biocompatible mitochondria-targeted nanocarriers with promising potential for advanced delivery applications.