Enzyme-Activatable Polypeptide for Plasma Membrane Disruption and Antitumor Immunity Elicitation

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cancer Therapy

Background:

• Enzyme-instructed self-assembly of bioactive molecules can disrupt cellular structures.
• Targeted drug delivery systems are crucial for effective cancer treatment.

Purpose of the Study:

• To develop an alkaline phosphatase (ALP)-activatable hybrid molecule for targeted cancer therapy.
• To investigate the potential of in situ peptide fibrillation for cytomembrane disruption and immune stimulation.

Main Methods:

• Synthesis of an indocyanine green (ICG)-CF4KYp hybrid activated by ALP.
• Utilizing hollow manganese dioxide (MnO2) nanospheres for targeted delivery.
• Assessing cytomembrane damage, oxidative stress, and immune response in vitro and in vivo.

Main Results:

• The hybrid molecule self-assembles into nanofibrils upon ALP activation, causing mechanical and oxidative damage to cancer cell membranes.
• MnO2 nanospheres facilitated targeted delivery and release of the therapeutic agent.
• The treatment induced immunogenetic cell death, enhancing anti-tumor immunity by promoting dendritic cell maturation and CD8+ T cell infiltration.

Conclusions:

• The developed cytomembrane injury strategy holds promise for lesion-specific elimination of primary, abscopal, and metastatic tumors.
• This approach may inspire new bioinspired nanoplatforms for anticancer theranostics.