Tannic Acid-Assisted Biomineralization Strategy for Encapsulation and Intracellular Delivery of Protein Drugs

Abstract

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.

Calcium Carbonate-Based Nanoplatforms for Cancer Therapeutics: Current State of Art and Future Breakthroughs

“…Nanocarriers have several potential advantages in drug delivery: , (i) biocompatibility without significant toxicity or immune response; (ii) biodegradability in biological environments; (iii) responsiveness to low pH; (iv) easily available at low cost; and (v) stable biochemical properties that do not affect the biological activity of the payload. Due to cost-effectiveness, biosafety, biodegradability, and pH sensitivity, , CaCO 3 NPs can carry a variety of drugs that have killing effects on tumors, such as targeted drugs, nontargeted drugs, and genes. , They have good drug loading capacity and can maintain good drug stability.…”

“…Due to cost-effectiveness, biosafety, biodegradability, and pH sensitivity, 48 , 49 CaCO 3 NPs can carry a variety of drugs that have killing effects on tumors, such as targeted drugs, nontargeted drugs, and genes. 50 , 51 They have good drug loading capacity and can maintain good drug stability.…”

Glucose oxidase and metal catalysts combined tumor synergistic therapy: mechanism, advance and nanodelivery system

“…In addition to the above, biomineralization-based nanoparticles can take on other forms. Through biomineralization, GOx can also be combined with zero-valent iron or Mn 2+ to achieve ST/CDT or IMT/ST synergistic modes [ 134 ]. These formulations also demonstrated promising outcomes.…”