A biomimetic camouflaged metal organic framework for enhanced siRNA delivery in the tumor environment.

Gene silencing through RNA interference (RNAi), particularly using small double-stranded RNA (siRNA), has been identified as a potent strategy for targeted cancer treatment. Yet, its application faces challenges such as nuclease degradation, inefficient cellular uptake, endosomal entrapment, off-target effects, and immune responses, which have hindered its effective delivery. In the past few years, these challenges have been addressed significantly by using camouflaged metal-organic framework (MOF) nanocarriers. These nanocarriers protect siRNA from degradation, enhance cellular uptake, and reduce unintended side effects by effectively targeting desired cells while evading immune detection. By combining the properties of biomimetic membranes and MOFs, these nanocarriers offer superior benefits such as extended circulation times, enhanced stability, and reduced immune responses. Moreover, through ligand-receptor interactions, biomimetic membrane-coated MOFs achieve homologous targeting, minimizing off-target adverse effects. The MOFs, acting as the core, efficiently encapsulate and protect siRNA molecules, while the biomimetic membrane-coated surface provides homologous targeting, further increasing the precision of siRNA delivery to cancer cells. In particular, the biomimetic membranes help to shield the MOFs from the immune system, avoiding unwanted immune responses and improving their biocompatibility. The combination of siRNA with innovative nanocarriers, such as camouflaged-MOFs, presents a significant advancement in cancer therapy. The ability to deliver siRNA with precision and effectiveness using these camouflaged nanocarriers holds great promise for achieving more personalized and efficient cancer treatments in the future. This review article discusses the significant progress made in the development of siRNA therapeutics for cancer, focusing on their effective delivery through novel nanocarriers, with a particular emphasis on the role of metal-organic frameworks (MOFs) as camouflaged nanocarriers.

Heat sensitive E-helix cut ferritin nanocages for facile and high-efficiency loading of doxorubicin.

Ferritin possesses a stable and uniform cage structure, along with tumor-targeting properties and excellent biocompatibility, making it a promising drug delivery vehicle. However, the current ferritin drug loading strategy involves complex steps and harsh reaction conditions, resulting in low yield and recovery of drug loading, which limits the clinical application prospects of ferritin nanomedicine. In this study, we utilized the high-efficiency heat-sensitivity of the multiple channel switch structures of the E-helix-cut ferritin mutant (Ecut-HFn) and Cu2+ assistance to achieve high-efficiency loading of chemotherapeutic drugs in a one-step process at low temperatures. This method features mild reaction conditions (45 °C), high loading efficiency (about 110 doxorubicin (Dox) per Ecut-HFn), and improved protein and Dox recovery rates (with protein recovery rate around 94 % and Dox recovery rate reaching up to 45 %). The prepared ferritin-Dox particles (Ecut-HFn-Cu-Dox) exhibit a uniform size distribution, good stability, and retain the natural tumor targeting ability of ferritin. Overall, this temperature-controlled drug loading strategy utilizing heat-sensitivity ferritin mutants is energy-saving, environmentally friendly, efficient, and easy to operate, offering a new perspective for scaling up the industrial production of ferritin drug carriers.