Stimuli-responsive (nano)architectures for phytochemical delivery in cancer therapy.

The use of phytochemicals for purpose of cancer therapy has been accelerated due to resistance of tumor cells to conventional chemotherapy drugs and therefore, monotherapy does not cause significant improvement in the prognosis and survival of patients. Therefore, administration of natural products alone or in combination with chemotherapy drugs due to various mechanisms of action has been suggested. However, cancer therapy using phytochemicals requires more attention because of poor bioavailability of compounds and lack of specific accumulation at tumor site. Hence, nanocarriers for specific delivery of phytochemicals in tumor therapy has been suggested. The pharmacokinetic profile of natural products and their therapeutic indices can be improved. The nanocarriers can improve potential of natural products in crossing over BBB and also, promote internalization in cancer cells through endocytosis. Moreover, (nano)platforms can deliver both natural and synthetic anti-cancer drugs in combination cancer therapy. The surface functionalization of nanostructures with ligands improves ability in internalization in tumor cells and improving cytotoxicity of natural compounds. Interestingly, stimuli-responsive nanostructures that respond to endogenous and exogenous stimuli have been employed for delivery of natural compounds in cancer therapy. The decrease in pH in tumor microenvironment causes degradation of bonds in nanostructures to release cargo and when changes in GSH levels occur, it also mediates drug release from nanocarriers. Moreover, enzymes in the tumor microenvironment such as MMP-2 can mediate drug release from nanocarriers and more progresses in targeted drug delivery obtained by application of nanoparticles that are responsive to exogenous stimulus including light.

Epigenetic regulation of autophagy by non-coding RNAs in gastrointestinal tumors: Biological functions and therapeutic perspectives.

Cancer is the manifestation of changes and mutations in genetic and epigenetic levels. Non-coding RNAs (ncRNAs) are commonly dysregulated in disease pathogenesis, and their role in cancer has been well-documented. The ncRNAs regulate various molecular pathways and mechanisms in cancer that can lead to induction/inhibition of carcinogenesis. Autophagy is a molecular "self-digestion" mechanism its function can be pro-survival or pro-death in tumor cells. The aim of the present review is to evaluate the role of ncRNAs in regulating autophagy in gastrointestinal tumors. The role of the ncRNA/autophagy axis in affecting the progression of gastric, liver, colorectal, pancreatic, esophageal, and gallbladder cancers is investigated. Both ncRNAs and autophagy mechanisms can function as oncogenic or onco-suppressor and this interaction can determine the growth, invasion, and therapy response of gastrointestinal tumors. ncRNA/autophagy axis can reduce/increase the proliferation of gastrointestinal tumors via the glycolysis mechanism. Furthermore, related molecular pathways of metastasis, such as EMT and MMPs, are affected by the ncRNA/autophagy axis. The response of gastrointestinal tumors to chemotherapy and radiotherapy can be suppressed by pro-survival autophagy, and ncRNAs are essential regulators of this mechanism. miRNAs can regulate related genes and proteins of autophagy, such as ATGs and Beclin-1. Furthermore, lncRNAs and circRNAs down-regulate miRNA expression via sponging to modulate the autophagy mechanism. Moreover, anti-cancer agents can affect the expression level of ncRNAs regulating autophagy in gastrointestinal tumors. Therefore, translating these findings into clinics can improve the prognosis of patients.