Nanoparticle-based Drug and Gene Delivery for Anti-Cancer Therapy

Nanoparticle-mediated drug delivery systems have emerged as highly adaptable platforms capable of integrating
multiple therapeutic modalities into a single system. By combining precise targeting, enhanced cellular uptake, and
controlled release, these platforms enable advanced strategies in cancer therapy, including targeted protein
degradation, photodynamic therapy, and adoptive immune cell modulation.
In this study, we explore innovative nanoplatforms that exemplify this versatility. First, we present a polymeric
nanoparticle system in which the polymer itself acts as a degrader, unifying the functions of drug and delivery
vehicle to efficiently degrade oncogenic protein. This self-assembling nanoparticle demonstrated effective tumor
accumulation and significant tumor suppression in vivo. Furthermore, leveraging the gene delivery capacity of
nanoparticles, we developed CAPRN for in situ anti-PD-L1 antibody production with laser-triggered release, and a
lipopolyplex-based system (pUnivody@LPP-PBA) to express Fc fragments on tumor cells, thereby activating
natural killer (NK) cells in an antigen-independent manner. In vivo experiments confirmed that these smart
delivery systems effectively reprogrammed the tumor microenvironment by enhancing T cell infiltration, activating
NK cells, and inducing potent anti-tumor immune responses across multiple cancer models.
Overall, these findings highlight the potential of multifunctional nanoparticles as active therapeutic agents capable
of gene delivery, protein degradation, and immune modulation, offering a promising platform for next-generation
precision cancer nanomedicine.