Nanotechnology in Theranostics and Nutraceuticals intervention for GI cancers

Microsatellite Instability (MSI) triggered by DNA mismatch repair deficiency is a crucial prognostic as well as predictive biomarker in GI cancers.

Gastrointestinal (GI) cancer, the 5th most common malignancy involving epigenetic, genetic, and environmental factors with high rate of human demise, still remains a daunting challenge to be circumvented. Of many, Microsatellite Instability (MSI) triggered by DNA mismatch repair deficiency is a crucial prognostic as well as predictive biomarker in GI cancers. Moreover, tumour genotyping and activation of signalling pathways like RAS/BRAF, PI3K, WNT, and ß-catenin stat3 also play significant roles in progression of the disease. Epigenetic regulation of MYC-mediated differentially expressed genes in gastric cancer cell lines has also shed some light developing new therapeutic targets in GI cancers. When validated adequately, sentinel lymph node (SLN) navigation surgery can substantially influence the treatment of gastric cancer giving rise to the conditions for targeted and effective lymphadenectomies.

As we behold, it can avowedly be stated that nanoparticles (NPs), manipulated rightly with suitable physico-chemical properties such as type of the matrix, polarity, size, charge, surface chemistry, etc., have extensively been explored with its far-reaching ramifications in theranostics (both diagnosis and therapy) of GI cancers. For oral-esophageal cancer, non-toxic Au-NPs with improved MRI contrast and paclitaxel loaded folate targeted polymeric micelles have been synthesized. For gastric cancer, molecular theranostic target being Her2neu, magnetic Fe-NP, fluorescent NPs, polypeptide NPs, PEG-PEI liposomes, ursolic acid NPs, paclitaxel and tetrandrine co-encapsulated NPs have been generated and tested. For liver cancer, Au-nanocages, Cellax, Mn-SPIO, etc. have been explored. Photodynamic therapy with targeted photofrin and magnetic thread implants with ferrous oxide NPs coupled to 5-FU are investigated in gallbladder cancer. To combat pancreatic cancer (somatostatine receptors being explored as molecular theranostic), Au-coated iron oxide NPs, various gemcitabine NPs, Radio-labelled PEGylated liposomal NPs, liposomal zoledronate, etc. are studied as possible arsenals. Modalities for colon cancer (KRAS as target) include theranostic iron oxide NPs, mesoporous silica NPs, paclitaxel loaded onto chitin polymer NPs, amphiphilic hydrogels loaded with doxorubicin, cholesteryl butyrate solid lipid NPs, etc.

Much to our intrigue, numerous functional foods have exhibited their potential to protect against or increase risk for gastrointestinal (GI) cancers, including their methods of preparation and habits of consumption. The chemopreventive mechanisms by which fruits and vegetables (~400 g/day) reduce esophageal and stomach cancer risk might be attributed to the presence of high levels of micronutrients including antioxidants (vitamin C and E, β-carotene, selenium, and others) which can decrease DNA damage by scavenging reactive oxygen species (ROS) and flavones which inhibit carcinogenesis by decreasing focal adhesion kinases and metalloproteinases. Perhaps the strongest data in support of micronutrient supplementation and upper GI malignancies come from a trial of 29,584 participants in Linxian, China where participants who received 15 mg β-carotene, 50 μg selenium, and 30 mg α-tocopherol daily for 5.25 years had shown a lower risk of gastric cancer at the end of the trial and after an additional 10 -year post-supplementation follow-up period (HR, 0.89). On the other hand, consumption of red or processed meat has been linked to increased risk of GI cancers. Consumption of extremely hot beverages is associated with esophageal cancer risk. Abusive consumption of alcoholic beverages leads to public health problems that include direct effects on the consumer (liver disease, motor vehicle accidents, increased cancer risk) albeit the association between alcohol consumption and cancer risk is complex. A wide range of controversial evidences are available for vitamin

D intake and risk of GI cancers. Therefore, prospective, controlled trials are needed to study the effects of diets on GI cancers.

There is no denying the fact that the journey of nanomedicine, with all its proven sovereignty, has already begun for delivering food supplements such as fatty acids, bioactive peptides, micronutrients, phytochemicals, etc. with higher bioavailability. At EON, we are now focusing on various novel approaches to develop a diverse range of nano-formulations to fortify edible products with efficacious active ingredients with guaranteed stability of the actives therein. Needless to mention, these nanomaterials will be thoroughly investigated for their cytotoxicity on GI cancers and would be used advisedly. Nonetheless, attention should be paid to eliminate possible adverse effects complying with the guidelines, regulations, and directives issued by EU and USFDA.