Size-Transformable Hyaluronan Stacked Self-Assembling Peptide Nanoparticles for Improved Transcellular Tumor Penetration and Photo-Chemo Combination Therapy

Size-transformable nanomedicine has the potential to overcome systemic and local barriers, leading to efficient accumulation and penetration throughout the tumor tissue. However, the design of such type of nanomedicine was seldom based on active targeting and intracellular size transformation. Here, we report an intracellular size-transformable nanosystem, in which small and positively charged nanoparticles (< 30 nm) prepared from the self-assembly of an amphiphilic hexadecapeptide derivative was coated by folic acid and dopamine decorated hyaluronan (HA) to form large and negatively charged nanoparticles (~ 130 nm). This nanosystem has been proven to improve the blood circulation half-life of the drug and prevent premature intravascular drug leakage from the nanocarrier. Once accumulated in the tumor, the nanoparticles were prone to HA and folic acid mediated cellular uptake, followed by intracellular size-transformation and discharge of transformed small nanoparticles. The size-transformable nanosystem ...