Tumor microenvironment participates in all stages of tumor progression and has emerged as a promising therapeutic target for cancer therapy. Rapid progress in the field of molecular self-assembly using various biological molecules has resulted in the fabrication of nanoformulations, specifically targeting and regulating the microenvironment components to inhibit tumor malignancies. This inhibition process is based on the differentiating biophysicochemical cues guiding tumor and normal tissue microenvironments. Peptides and peptide derivatives, owing to their great biocompatibility, chemical versatility, bioactivity, environmental sensitivity and biological recognition abilities, have been widely utilized as building blocks to construct multifunctional nanostructures for targeted drug delivery and controlled release. Several groups of peptides have been identified with the ability to penetrate plasma membranes, to regulate the essential signaling pathways of angiogenesis and immune reactions, and to recognize some key components in tumor microenvironment such as the vascular systems, stromal cells, and abnormal tumor biophysicochemical features. Thus, as different modules, these various functional peptides and their derivatives can be integrated into nanoformulations specifically targeting tumor microenvironment with an increased selectivity, on-demand responsivity, elevated cellular uptake, and improved tumor therapy. In this review, we introduce several groups of functional peptides, and highlight peptide-based nanoformulations that specifically target tumor microenvironment, followed by our perspective on the development of smart drug delivery systems with enhanced therapeutic efficacy.
- Gene delivery systems
- Pharmacokinetics, metabolism and activation
- Membrane targets
- The American Society for Pharmacology and Experimental Therapeutics