Protein therapy has been considered to be one of the
most direct
and safe ways to regulate cell function and treat tumors. However,
safe and effective intracellular delivery of protein drugs is still
a key challenge. Herein, we developed a tannic acid-assisted biomineralization
strategy for the encapsulation and intracellular delivery of protein
drugs. RNase A and glucose oxidase (GOD) were choose as the protein
drug model. RNase A, GOD, TA, and Mn2+ are mixed in one
pot to attain RG@MT, and CaCO3 coating is subsequently
carried out to construct RG@MT@C through biomineralization. Once RG@MT@C
is endocytosed, the acidic environment of the lysosome will dissolve
the protective layer of CaCO3 and produce plenty of CO2 to cause lysosome bursting, ensuring the lysosome escape
of the RG@MT@C and thus releasing the generated TA-Mn2+, RNase A, and GOD into the cytoplasm. The released substances would
activate starvation therapy, chemodynamic therapy, and protein therapy
pathways to ensure a high performance of cancer therapy. Due to simple
preparation, low toxicity, and controlled release in the tumor microenvironment,
we expect it can realize efficient and nondestructive delivery of
protein drugs and meet the needs for precise, high performance of
synergistically antitumor therapy in biomedical applications.