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Polyethylenimine-CO2 adduct templated CaCO3 nanoparticles as anticancer drug carrier

Luo Wenli,Li Zhaojian,Zhang Ling,Xie Xingyi

Background Due to their porous structure and capability to degrade under acidic conditions, CaCO3 nanoparticles in vaterite form can be used as carriers to effectively deliver drugs to low-pH sites such as tumors. The usually used intravenous administration requires long-term vaterite phase and colloidal stability for storage and blood circulation. While passive accumulation in tumors can be achieved via the enhanced permeation and retention effect, active accumulation requires reactive groups on vaterite nanoparticles to conjugate targeting molecules. Both requirements are hard to achieve in one simple and economical vaterite formulation. Herein, we used polyethylenimine (PEI)-based CO2 adduct as both a CO2 source and a template for vaterite mineralization to generate PEI-CO2@CaCO3 colloidal particles, with reactive amino groups from the PEI template.Results The obtained nanoparticles with a hydrodynamic diameter of 200–300 nm have a vaterite phase and colloidal stability in an aqueous solution for over 8 months. These nanoparticles could effectively load anticancer drug doxorubicin via coprecipitation and be surface-modified with polyethylene glycol (PEG) and folic acid for long-term blood circulation and tumor targeting purposes, respectively. After being endocytosed, the PEI-CO2 adduct accelerates the dissolution of drug-loaded nanoparticles to generate CO2 bubbles to break the lysosomes, leading to rapid doxorubicin delivery inside tumor cells. The degradation of PEI-CO2 in the CaCO3 nanoparticles could also release PEI and CO2 and may contribute to the disruption of normal cellular functions. As a result, the drug-loaded PEI-CO2@CaCO3 nanoparticles strongly suppressed tumor growth in mice with HeLa tumor xenografts.Conclusion sA new and effective vaterite drug carrier for anticancer therapy has been developed using PEI-CO2 adduct as both a CO2 source and vaterite template for CaCO3 mineralization. This delivery system illustrates an application of CO2 generation materials in drug delivery and has the potential for further development.