Discovery Uncovers Novel Challenge for Nanotechnology-Based Treatments

Researchers from The University of Texas MD Anderson Cancer Center have made a significant discovery indicating that specific nano-based cancer therapies may exhibit reduced efficacy in younger patients. This finding underscores the imperative need for further exploration into how aging impacts the body’s ability to respond to treatments.

The investigation revealed that age-related disparities stem from the varying efficiency with which the liver filters the bloodstream. Younger livers demonstrate higher proficiency in this filtration process, which serves to minimize toxins in the blood but also strains out beneficial treatments, potentially rendering them ineffectual.

This groundbreaking study, published in Nature Nanotechnology on September 18, was spearheaded by Dr. Wen Jiang, M.D., Ph.D., Associate Professor of Radiation Oncology, and Dr. Betty Kim, M.D., Ph.D., Professor of Neurosurgery.

Dr. Jiang elucidated, “In simple terms, our liver is designed to protect us, but in the case of young individuals, it might inadvertently hinder the effectiveness of nanotherapies. Although there is currently substantial interest in nano-scale delivery systems and designs, the role of age in the efficiency of these systems has largely been overlooked. In preclinical models, younger livers are so proficient that they filter out a substantial portion of the nanomedicine. Consequently, these drugs may, in certain scenarios, be less potent in younger patients compared to their older counterparts.”

In contrast to conventional cancer therapies, which involve the direct administration of medication into the body, nanomedicines employ nano-scale carriers to transport treatments. The advantages of nanomedicine formulations include reduced toxicity, heightened specificity in targeting, and the potential for increased dosages, depending on the treatment’s objectives.

To date, the Food and Drug Administration has sanctioned over 50 nano-based therapies, with the National Cancer Institute currently endorsing 19 of them for cancer treatment. The study in question employed nanoparticle-albumin-bound paclitaxel, a medication used since 2005 for specific refractory or recurrent cancers.

While scientists do not fully comprehend the mechanisms governing how the liver filters the bloodstream, prior research has indicated a link between the clearance rate and the presence of the scavenger receptor MARCO. Younger Kupfer cells, the immune cells residing in the liver, express this protein more abundantly.

After confirming the contrasting outcomes between young and aged models, the team explored the prospect of therapeutic blockade of MARCO as a strategy to prevent drug clearance. This blockade mitigated the uptake of the nanomedicine and bolstered its antitumor effects, but only in the younger models.

Dr. Jiang emphasized that this study, although centered on cancer, addresses a potential obstacle for any nanodrug delivery system. He elaborated that various proteins, antibodies, and viruses possess distinct clearance mechanisms, but the crux of the matter lies in the liver.

In conclusion, this groundbreaking research underscores the need for tailored drug delivery strategies that consider individual patient populations, and it encourages further exploration of the clearance process and strategies to overcome it.

Source: University of Texas M. D. Anderson Cancer Center

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