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Researchers developed enzyme-responsive polypeptides for targeted drug delivery. These polypeptides change structure in response to tumor enzymes, enabling controlled drug release and cancer cell targeting for improved therapeutic outcomes.

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Area of Science:

  • Biomaterials Science
  • Polymer Chemistry
  • Nanotechnology

Background:

  • Secondary structure control in polypeptide materials is crucial for regulating their properties and functions.
  • Biomedical applications require materials capable of changing their functions *in situ*.

Purpose of the Study:

  • To design and construct enzyme-responsive polypeptides as gating materials for mesoporous silica nanoparticles (MSNs).
  • To achieve cancer-selective drug release and cellular internalization by modulating polypeptide secondary structure.

Main Methods:

  • Conjugating enzyme-responsive polypeptides onto the surface of MSNs.
  • Utilizing the structural transition of polypeptides triggered by alkaline phosphatase (ALP) overproduced by tumor cells.
  • Observing the change from a negatively charged, distorted, flexible conformation to a positively charged, α-helical, rigid conformation.

Main Results:

  • The polypeptide-gated MSNs prevented premature drug leakage due to the flexible conformation covering the pores.
  • Upon encountering tumor-specific ALP, polypeptides transitioned to a rigid, α-helical structure, uncovering the pores.
  • This transition facilitated targeted drug release and enhanced cellular internalization, leading to efficient tumor cell killing.

Conclusions:

  • Polypeptide chain flexibility plays a critical role in modulating biological function.
  • Enzyme-responsive secondary structure transitions offer a novel strategy for targeted drug delivery systems.
  • This work presents a new application paradigm for synthetic polypeptides in cancer therapy.