A multifaceted pathophysiological cascade associated with numerous genes, pathways and factors makes cancer a grave and sometimes fatal condition that impacts millions of lives. Given its intricate nature, it is the second greatest cause of death globally, putting at risk human health and survival. The American Cancer Society anticipates close to 13 million deaths and ∼21.6 million new instances will be reported by 2030, inflicting a significant burden on healthcare systems.[1], [2] Current interventions hinge on chemotherapy, radiation therapy and surgical methods, with some clinical efficacy. However, these approaches have also resulted in catastrophic impacts attributed to the tumor’s dynamic, agile and resilient growth trajectory. In particular, substantial toxicities, low target specificity and potential for resistance have made it challenging for healthcare professionals to combat cancer.[3], [4], [5] Consequently, in the realm of onco-based curative actions, devising novel therapeutic strategies that might exclusively hone tumor-specific chemical alteration while offering and enabling drug delivery is deemed worthwhile.[6], [7], [8] Indeed, cancer cells demonstrate enhanced cellular proliferation and quick expansion, which increases their reliance on ‘nutrients’ to sustain themselves for the synthesis of macromolecules: nucleic acids, lipids, proteins and peptides, for the generation of metabolic energy. The nutrients that fuel the biochemical engine within tumor cells include glucose, amino acids, fatty acids (FAs), vitamins and micronutrients like trace metals. It is paramount to tap into distinct nutrient transporters (NTs), given that most of these molecules are hydrophilic and unlikely to transit all over the plasma membrane. Conversely, neovascularization among cancer cells fosters blood-borne nutrient accessibility, which upregulates the NTs, thus synchronizing their supply and delivery for cancer cells to satisfy the latter’s greater nutrient demand.[9], [10], [11]
A deficit distinctive to cancer cells entails that interfering with the accessibility of nutrients could be discretely fatal to them. In essence, the underlying notion is apparent and rational. By impeding the inflow of vital nutrients to tumor cells and their accessibility, it could be possible to starve the cells to death. Hence, with an eye on nutrition intake within tumors, particularly NTs, it has become an intriguing research domain for oncotherapeutic intervention. Indeed, there have been notable breakthroughs in curating cancer lately. Of particular note is the deployment of novel functional nanocarriers for targeting cancer cells, which has drawn the interest of researchers. By designing NT-targeted nanodrug delivery vehicles, it is possible to further enhance the specificity and efficacy of these nanovehicles to cancerous cells. By tweaking their surface with NT-specific substrates, it is plausible to strengthen their recognition and delivery to the tumors. Consequently, the past few decades have witnessed novel insights into their role in arresting tumor progression besides other key facets, like cancer cell dissemination, metastasis and vasculogenesis.[12], [13], [14], [15] The key thrust of this review is to comprehend the several in silico, in vitro and in vivo investigations reported in scientific literature relying on selectively targeting NTs. As part of this review, nano-assisted procedures effectively deployed for focusing NT-guided cancer cells have also been listed. In a nutshell, the article summarizes recent progress in cytotoxic capacity by NTs, which could assist in oncotherapy.
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