Functional metal–organic framework nanoparticles loaded with polyphyllin I for targeted tumor therapy

Polyphyllin I (PPI) is a naturally active steroidal saponin that has good therapeutic effects in various cancers, such as liver and lung cancers. However, owing to its non-selective distribution in various tissues, it is toxic and has side effects on normal human organs while taking effect. To solve this problem, a unique functionalized nanomaterial called metal–organic frameworks (MOFs) was prepared as a targeted nanoparticle for tumor therapy. MOFs are porous coordination polymers that can achieve precise structural and functional adjustability by regulating the organic ligands and metal ions. IRMOF-8 with a multidimensional network topology whose aperture matched the size of PPI was selected to load the PPI. In this study, PPI was loaded into IRMOF-8 via ex situ encapsulation. Drug-loaded nanoparticles (NPs) were coated with polyethylene glycol (PEG) coupled to cell-penetrating peptides (CPPs). The obtained nanoplatform denoted as PEG-CPP44/PPI@IRMOF-8 NPs had a spherical shape, a rough and uneven surface, an average particle size of 202.97 nm, excellent drug loading (33.37%), and showed release behavior. In addition, the NPs showed remarkable targeting selectivity for cellular uptake and in vivo imaging. More importantly, it exhibited good antitumor activity in vivo and in vitro. It not only increased the therapeutic efficiency of PPI for liver cancer but also reduced the damage caused by PPI to normal organs. The preparation of the functional nanoplatform (PEG-CPP44/PPI@IRMOF-8) shows the advantages and highlights of MOF-based drug delivery systems and can help in the follow-up precise treatment of tumors.