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Area of Science:

  • Biomaterials science
  • Chemical biology
  • Biomedical engineering

Background:

  • Biomolecular condensates are vital for cellular organization and biomedicine.
  • Limited pH stability of condensates restricts their use in diverse physiological settings.
  • Developing pH-stable biomolecular systems is crucial for advanced biomedical applications.

Purpose of the Study:

  • To engineer tunable coacervates from simple amino acids with broad pH stability.
  • To investigate the thermoresponsive properties of these novel amino acid-based coacervates.
  • To demonstrate the potential of pH-stable coacervates for in vivo drug delivery and therapy.

Main Methods:

  • A molecular shielding strategy was employed to modify terminal ionizable groups of amino acids.
  • Selective modification was used to create phase behavior independent of environmental pH.
  • Coacervates were characterized for pH stability, thermoresponsive transitions (LCST/UCST), and in vivo performance.

Main Results:

  • Tunable coacervation of simple amino acids was achieved over a wide pH range (1.0-13.0).
  • The amino acid-based coacervates exhibited distinct thermoresponsive behaviors (LCST or UCST).
  • N-terminal shielded phenylalanine coacervates demonstrated stability in gastric conditions and prolonged gastrointestinal drug retention.

Conclusions:

  • Molecular shielding offers a method to create pH-independent amino acid coacervates.
  • These programmable coacervates possess tunable thermoresponsive features for tailored applications.
  • The study demonstrates successful in vivo oral drug delivery and therapy for acute colitis, highlighting potential for biomedical applications.