Recent advances in targeted drug delivery systems for resistant colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the deadliest cancers in the world, the incidences and morality rate are rising and poses an important threat to the public health. It is known that multiple drug resistance (MDR) is one of the major obstacles in CRC treatment. Tumor microenvironment plus genomic instability, tumor derived exosomes (TDE), cancer stem cells (CSCs), circulating tumor cells (CTCs), cell-free DNA (cfDNA), as well as cellular signaling pathways are important issues regarding resistance. Since non-targeted therapy causes toxicity, diverse side effects, and undesired efficacy, targeted therapy with contribution of various carriers has been developed to address the mentioned shortcomings. In this paper the underlying causes of MDR and then various targeting strategies including exosomes, liposomes, hydrogels, cell-based carriers and theranostics which are utilized to overcome therapeutic resistance will be described. We also discuss implication of emerging approaches involving single cell approaches and computer-aided drug delivery with high potential for meeting CRC medical needs.

Significance of PSCA as a novel prognostic marker and therapeutic target for cancer

“…Colorectal cancer is a cancer that develops in the colon or rectum. This cancer typically affects the elderly, but it can occur at any age [ 93 ]. CRC usually first appears in the colon as small masses of noncancerous (benign) cells called polyps.…”

“…Colorectal cancer is one of the most common cancers. Genomic and epigenetic alteration, environmental and genetic factors are effective factors in the development of CRC [ 93 – 95 ].…”

Application of artificial intelligence in diagnosis and treatment of colorectal cancer: A novel Prospect

“…Abnormal mutations in genes and chromosomes can also cause drug resistance, which brings many obstacles to the treatment of CRC. In such an environment, the targeted therapy through drug delivery platform will contribute to precision medicine in the future ( 22 , 151 ). Russo et al used AI-based prediction model to analyze the patients who may have drug resistance before and after treatment.…”

“…Among them, DL and CNN are representatives of the most successful algorithms used in medicine in recent years ( 17 , 18 ). They play a very broad role in data management ( 19 ), information control ( 20 ), diagnosis prediction ( 21 ), and drug delivery ( 22 ). The branches of physics mainly include medical equipment ( 23 ) and robot applications, such as da Vinci robot system, which is widely used today ( 24 , 25 ).…”

Tumor microenvironment penetrating chitosan nanoparticles for elimination of cancer relapse and minimal residual disease

“…Despite all advancements in drug delivery strategies developed for targeting solid tumors, efficacy is still suboptimal due to numerous biological barriers, including endothelial, cell membrane, organelle membrane, and the nanoparticle's ability for on-target/off-target recognition, penetration, localization, concentration, and homogenous distribution. Most of these bottlenecks for successful NP delivery originate from the nature of the solid tumor microenvironment (TME), including the ability of immune editing, hypoxia, cancer stem cells (CSCs), extracellular matrix (ECM) components, and heterogeneity, among others (1,2). TME leverages inherent resistance mechanisms such as hypoxia and pH gradients and acquired resistance mechanisms such as clonal evolution and heterogeneity after surgery or chemotherapy.…”