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Smart biotherapeutics utilize dynamic covalent chemistry for targeted drug delivery. This study presents a pH-responsive protein assembly for selective cancer cell targeting and intracellular release, advancing nanomedicine.

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Area of Science:

  • Bioconjugation Chemistry
  • Nanomedicine
  • Drug Delivery Systems

Background:

  • Dynamic covalent chemistry offers a versatile approach for creating smart biotherapeutics by combining stable bonds with stimulus responsiveness.
  • Developing targeted drug delivery systems that can release therapeutic payloads intracellularly under specific conditions remains a significant challenge.

Purpose of the Study:

  • To design and construct a dynamic covalent protein assembly for selective cancer cell targeting and pH-triggered intracellular release.
  • To demonstrate the synergistic action of modular components in a novel nanomedicine platform.

Main Methods:

  • Utilized boronic acid/salicylhydroxamate chemistry for self-assembly of an active enzymatic protein core (cytochrome c) with cancer cell targeting motifs (somatostatin).
  • Performed bioorthogonal assembly under neutral aqueous conditions.
  • Investigated pH-dependent release of the protein under acidic conditions mimicking cellular uptake.

Main Results:

  • Successfully created a minimalistic, self-assembled protein construct with selective targeting capabilities.
  • Demonstrated rapid, bioorthogonal assembly under neutral pH.
  • Confirmed initiation of protein release under acidic pH conditions, characteristic of intracellular vesicles.

Conclusions:

  • The developed dynamic covalent strategy enables the creation of smart biotherapeutics with precise control over assembly and release.
  • This modular approach shows broad applicability for advancing nanomedicine and targeted therapeutic strategies.
  • The synergistic integration of targeting and stimulus-responsive release offers a promising platform for future drug development.