Bowel cancer survival rates could be improved if chemotherapy drugs were delivered via tiny nanoparticles to the diseased organs rather than oral treatment. That’s the conclusion of Indian and Australian scientists who have undertaken a study using nanoparticles to target bowel cancer, the third most common cancer in the world and the second most deadliest.
The researchers have shown in animal experiments that nanoparticles containing the chemotherapy drug Capecitabine (CAP) attach themselves directly to the diseased cells, bypassing healthy cells and therefore reducing toxic side effects as well as the size and number of tumors.
The scientists, from the Manipal Academy of Higher Education, the Indian Institute of Science, and the University of South Australia (UniSA), published their findings (“Chitosan-glucuronic acid conjugate coated mesoporous silica nanoparticles: A smart pH-responsive and receptor-targeted system for colorectal cancer therapy”) in Carbohydrate Polymers.
“Glycosylated pH-sensitive mesoporous silica nanoparticles (MSNs) of capecitabine (CAP) were developed for targeting colorectal cancer. The MSNs possessed an average pore diameter of 8.12 ± 0.43 nm, pore volume of 0.73 ± 0.21 cm3/g, and particle size of 245.24 ± 5.75 nm. A high loading of 180.51 ± 5.23 mg/g attributed to the larger pore volume was observed. The surface of the drug-loaded MSNs was capped with chitosan-glucuronic acid (CHS-GCA) conjugate to combine two strategies viz. pH-sensitive, and lectin receptor mediated uptake,” write the investigators.
“In vitro studies demonstrated a pH-sensitive and controlled release of CAP which was further enhanced in the presence of rat caecal content. Higher uptake of the (CAP-MSN)CHS-GCA was observed in HCT 116 cell lines. The glycosylated nanoparticles revealed reduction in the tumors, aberrant crypt foci, dysplasia and inflammation, and alleviation in the toxic features. This illustrated that the nanoparticles showed promising antitumor efficacy with reduced toxicity and may be used as an effective carrier against cancer.”
According to Sanjay Garg, Ph.D., professor of pharmaceutical science at UniSA, the sole Australian researcher involved in the project, CAP (otherwise known as Xeloda) is the first-line chemotherapy drug for bowel cancer. He co-supervised his colleagues from Manipal, India.
“Due to its short life, a high dose is necessary to maintain effective concentration, resulting in some harsh side effects when delivered conventionally, including severe hand and foot pain, dermatitis, nausea, vomiting, dizziness and loss of taste,” says Garg.
Exacerbated side effects
The side effects are exacerbated because the drug affects both healthy and diseased cells.
“A viable alternative to conventional therapy is targeted drug delivery using nanoparticles as smart carriers so that the drug can be delivered specifically to the tumor. This allows a smaller and less toxic dose,” he continues.
CAP delivered via nanoparticles reduces both the size and number of cancerous bowel tumors, results in fewer abnormal cells, improved red and white blood cell counts and less damage to other organs, explains Garg.
The targeted delivery system has a dual function: binding the receptors as well as releasing the drug to the tumor micro-environment.
“It has been a challenging project but we believe the platform technology developed can be applied to other cancers and chemotherapeutic drugs,” notes Garg.
Approximately two million people are diagnosed with bowel cancer each year and half of those are not expected to survive, according to the WHO. The risk factors include consuming processed meat, red meat and alcoholic drinks and obesity.