Granzyme B-mimetic nanozyme for nanovesicle targeted anticancer applications

Area of Science:

• Biochemistry
• Nanotechnology
• Immunotherapy

Background:

• Cytotoxic T lymphocytes are key in anti-tumour immunity, utilizing granzyme B (GrB) for cancer cell apoptosis.
• Mimicking T cell-based immunotherapy with GrB-like delivery systems is a promising but challenging therapeutic approach.

Purpose of the Study:

• To create a novel artificial metalloenzyme (nanozyme) with GrB-like protease activity for cancer therapy.
• To develop a nano-delivery system for targeted delivery and induction of apoptosis in tumour cells.

Main Methods:

• Engineered a nanozyme by site-specifically binding Palladium (Pd(II)) ions to human heavy chain apo-ferritin nanocages, forming a binuclear catalytic center.
• Encapsulated the Pd-ferritin complex within lipid nanoparticles displaying single-chain antibodies for targeted delivery.

Main Results:

• The nanozyme demonstrated GrB-like protease activity, inducing caspase-dependent apoptosis in cancer cells.
• The nanozyme-based nanovesicles achieved receptor-mediated delivery into tumour cell cytoplasm.
• Successfully mimicked T cell-mediated cytotoxicity for potential anti-cancer therapy.

Conclusions:

• The study presents a novel nanozyme with artificial GrB activity for cancer treatment.
• This nano-delivery system shows promise as a therapeutic option for solid tumours by inducing apoptosis.