Surface Self-Assembly of Dipeptides on Porous CaCO₃ Particles Promoting Cell Internalization

The self-assembling behavior of peptides and derivatives is crucial in the natural process to construct various architectures and achieve specific functions. However, the surface or interfacial self-assembly, in particular, on the surface of micro- or nanoparticles is even less systematically investigated. Here, uniform porous CaCO3 microparticles were prepared with different charged, hydrophobic and hydrophilic surfaces to assess the self-assembling behavior of dipeptides composed of various sequences. Experimental results indicate that dipeptides with a negative charge in an aqueous solution preferred to self-assemble on the hydrophobic and positively charged surface of CaCO3 particles, which can be ascribed to the electrostatic and hydrophobic interaction between dipeptides and CaCO3 particles. Meanwhile, the Log p (lipid–water partition coefficient) of dipeptides has a significant effect on the self-assembling behavior of dipeptides on the surface of porous CaCO3; dipeptides with high Log p preferred to self-assemble on the surface of CaCO3 particles, resulting in the improved cell internalization efficiency of particles with low cytotoxicity. After loading with a model drug (doxorubicin), the particles show obvious antitumor activity in animal experiments and can reduce Dox side effects effectively.