[Medicine Innovates] Revolutionizing Pancreatic Cancer Treatment: The Power of Stem-Cell-Membrane-Coated Nanotherapy - (관련 기사 click)

Pancreatic cancer, while not as prevalent as other cancers, stands out for its high lethality and is more common in men and older adults. It’s characterized by low survival rates, with an overall five-year survival rate around 10%, significantly dropping due to late-stage diagnosis common in many patients. The treatment landscape includes surgery, chemotherapy, radiation, and more recently, targeted and immunotherapies, though these are often limited to cases with specific genetic markers. However, the curative potential of these treatments is generally restricted to early-stage diagnoses, which are unfortunately rare. The difficulty in treating pancreatic cancer stems from several factors, including its late detection, often due to the absence of early symptoms and the pancreas’s deep abdominal location. Additionally, the cancer’s rapid growth and spread, combined with its resistance to conventional therapies, complicate treatment efforts. The lack of significant targetable mutations further challenges the development of effective treatments. Despite these hurdles, ongoing research into the disease’s biology and the advent of genomic and personalized medicine offers hope for future advancements in treatment and detection methodologies.

A new study published in Advanced Materials led by Professor Dongwoo Khang at Gachon University- South Korea together with colleagues: Jun-Young Park, Jun Young Park, Yong-Gyu Jeong, Joo-Hwan Park, Yeon Ho Park, and Sang-Hyun Kim developed a targeted therapeutic approach for pancreatic cancer, employing stem-cell-membrane-coated nanocarriers, referred to as “stemsomes,” for the delivery of anticancer drugs directly to tumor sites. The team engineered nanocarriers encapsulated within stem cell membranes, loaded with the anticancer drug doxorubicin. This involved isolating membranes from stem cells known for their tumor-homing capabilities and integrating them with nano-polylactide-co-glycolide (PLGA) particles containing doxorubicin. The authors characterized the physicochemical properties of the stemsomes, including size, charge, and drug encapsulation efficiency using techniques like dynamic light scattering and transmission electron microscopy. The researchers assessed the tumor-homing efficiency of the stemsomes in vitro using cancer cell lines. Confocal microscopy and flow cytometry were utilized to visualize and quantify the uptake of stemsomes by pancreatic cancer cells.

To understand the molecular mechanisms underlying the enhanced targeting capability of the stemsomes, RNA sequencing was performed on the tumor-educated stem cells. This provided insights into gene expression changes associated with the tumor-homing phenotype. The ultimate test of the stemsomes’ potential was conducted through in vivo experiments in mouse models of pancreatic cancer. The researchers administered the stemsomes to these models and monitored tumor progression using bioluminescence imaging and histological analyses.

The authors showed that stemsomes has a remarkable ability to encapsulate and protect the anticancer drug, ensuring its targeted delivery to pancreatic tumor cells while minimizing exposure to healthy tissues. The stem-cell-membrane-coated nanocarriers exhibited an intrinsic ability to home in on pancreatic tumors, effectively overcoming the challenge posed by the lack of specific surface markers on these cancer cells. RNA sequencing revealed significant changes in gene expression in the tumor-educated stem cells, highlighting the molecular adaptations that contribute to their tumor-homing capabilities. When the authors conducted in vivo studies they showed that the stemsome treatment led to a marked reduction in tumor size and proliferation, outperforming traditional chemotherapy approaches in terms of efficacy and safety.

The findings suggest that the stemsome platf types of tumors, especially those that are difficult to target with existing therapies. In summary, Professor Dongwoo Khang (Founder CEO of Ectosome Inc.) and colleagues reported a novel, targeted therapeutic strategy that leverages the natural tumor-homing ability of stem cells, encapsulated in a nanocarrier system, to deliver anticancer drugs directly to pancreatic cancer cells. This approach promises to enhance the efficacy of cancer treatment while reducing systemic toxicity, offering a new avenue for the development of personalized cancer therapeutics.

In certain aspects, stemsome emerges as a more practical solution compared to ADC anticancer drugs. This is because it eliminates the necessity for specific targeting information about cancers, relying solely on patient-derived cancer cells to educate the ligand expression on the membrane of stem cells. This versatility makes stemsome a promising and adaptable strategy in the fight against cancer.

Cover Legend: Utilizing patient-derived cancer cells for the assessment of therapeutic efficacy is a pioneering strategy to validate the potential of stemsome treatment. This innovative approach aims to address the challenge faced by a significant portion of pancreatic cancer patients who are unable to benefit from targeted anticancer drugs due to the absence of specific biomarkers on their cancer cells. The methodology involves the implantation of patient-derived cancer cells to demonstrate the effectiveness of stemsome within a short timeframe of 2-3 weeks. This accelerated timeline not only expedites the evaluation process but also holds promise for a more timely and personalized treatment option for individuals with pancreatic cancer, ultimately broadening the scope of viable therapeutic interventions (PCT patent #: WO2023/153832A1).