PH-responsive <italic>in vivo</italic> self-assembled biomaterials and their application for tumor diagnosis and therapy

Abstract

The passive targeting of self-assembled nanomaterials at tumor sites can improve drug delivery capability, which has great prospects in biomedical field. However, dynamically balanced self-assembled nanomaterials will interact with a variety of biological interfaces or biological macromolecules in vivo , and there are problems with structural instability, and it is difficult to achieve accurate control of their structure, which hampers their further clinical application. pH can affect the electrical charge of the amino acids, which affects the electrostatic interaction of polypeptides in the process of self-assembly, so changing the pH is one of the ways to regulate the process of self-assembly. In this way, we propose in vivo self-assembly strategy based on the pH-response peptide for tumor diagnosis and therapy. After reaching the tumor sites, the exogenous molecules structure will change under the stimulus of the acidic tumor microenvironment, and then form a highly ordered nanostructure, which can prolong the retention time of the material and improve the utilization effect. Starting from the design of small molecular peptides, polypeptides are combined with other functional biomolecules, and pH change at tumor sites is used to construct pH-responsive in vivo self-assembled materials. In this way, accurate and controllable diagnosis and therapy can be realized. The acidic tumor microenvironment is one of the most prominent characteristics of tumor microenvironment and is a good trigger for designing microenvironmental responsive molecules. Our group designed a pH-sensitive molecule BP-KLVFF-His6-PEG, the hydrophilic and hydrophobic balance was destroyed after reaching the acidic environment at the tumor site (pH 6.5). Driven by the hydrogen bonds of the KLVFF fragment, the molecule was self-assembled to form nanofibers. Combined with the imaging agent Nero red and doxorubicin, it can be used for long-term tumor imaging and enhancement to therapeutic efficacy. By combining functional molecules of tumor diagnosis and therapy with pH-responsive polypeptides, a more complex assembly system with biological functions can be constructed to improve the diagnostic function of imaging agents and the therapeutic effect of chemotherapy drugs. In this way, the new strategy of using pH-responsive polypeptides to build ordered assembly in vivo is paving the way for the development of nanomaterials for tumor diagnosis and therapy, which brings new hope for clinical application.