In the quest to improve targeted cancer treatments, a team of researchers led by Carmela Mazzacano from the Department of Pharmacy at the University of Salerno has made significant strides in the development of advanced nanocarriers for delivering small interfering RNA (siRNA) to colorectal cancer cells. Their work, published in the journal *Materials Today Advances* (translated to English as “Advanced Materials Today”), offers a nuanced look at how precise structural modifications can enhance the performance of polysaccharide-based vectors.
The study focuses on the systematic design and evaluation of a library of inulin-based graft copolymers for siRNA delivery. Inulin, a naturally occurring polysaccharide, was progressively modified through a modular strategy. The team first grafted branched polyethylenimine (bPEI) at two different densities, then introduced polylactic acid (PLA) segments to create amphiphilic copolymers, and finally conjugated folic acid (FA) as a targeting moiety for colorectal cancer (CRC) cells. This stepwise approach led to the development of eight structurally related copolymers, enabling a comprehensive investigation of how specific composition features affect nanoparticle formation, stability, biocompatibility, and transfection efficiency.
One of the most intriguing findings was the counterintuitive structure–function relationships observed. For instance, high bPEI density negatively impacted biological stability, while folic acid improved both colloidal and biological stability beyond its classical targeting function. “We were surprised to find that folic acid not only enhanced targeting but also played a crucial role in stabilizing the nanoparticles,” Mazzacano noted. This discovery could have significant implications for the design of future nanocarriers.
The amphiphilic nature imparted by PLA significantly influenced nanoparticle self-assembly, colloidal behavior, siRNA encapsulation, and release compared to PLA-free nanosystems. Nanoparticles demonstrated improved siRNA protection and transfection despite a reduced intracellular uptake, suggesting differences in intracellular trafficking and endosomal escape. A multi-omics analysis further revealed significant alterations corroborating the active internalization and confirming the safety of the treatment at the cellular level.
This research provides new insights into the fine structural tuning of polysaccharide-based vectors, offering valuable guidelines for next-generation nanocarriers. The findings could pave the way for more effective and targeted cancer therapies, potentially reducing side effects and improving patient outcomes. As Mazzacano explains, “Our work highlights the importance of precise structural modifications in enhancing the performance of nanocarriers, which could lead to more effective and targeted cancer treatments.”
The implications of this research extend beyond the immediate scope of colorectal cancer treatment. The principles and methodologies developed could be applied to other types of cancer and even non-cancerous diseases, making it a significant advancement in the field of nanomedicine. The study’s publication in *Materials Today Advances* underscores its relevance and potential impact on the scientific community and the broader healthcare industry.