Cancer is a leading cause of death globally, with rising prevalence and mortality rates. Cancer cells exhibit uncontrolled proliferation and require high nutrient intake for growth and survival. They achieve this by modifying metabolic pathways, including lipid, amino acid, and glucose metabolism. Traditional cancer treatments like chemotherapy and radiotherapy have limitations: drug resistance, lack of specificity leading to severe side effects, recurrence, and metastasis. Metabolic chemotherapy offers a therapeutic window, with polyamine metabolism emerging as a promising target. Recent research emphasizes the metabolic specificities of cancers, paving the way for novel treatment strategies, including the use of nanoparticles (NPs). This review examines cutting-edge nanomaterial approaches targeting distinct cancer metabolisms, comparing their advantages, challenges, and potential over conventional therapies.

The literature review covers various aspects of cancer metabolism and existing treatments. It discusses the reprogramming of metabolic pathways in cancer cells due to tumor suppressor loss and oncogene activation, focusing on glucose and glutamine metabolism. The review examines the roles of oncogenes like Ras and Myc in stimulating glucose and glutamine uptake and metabolism. It also details how cancer cells adapt to nutrient deprivation by scavenging extracellular proteins, amino acids from cell debris, and extracellular lipids. The importance of acetate and its metabolizing enzymes in cancer cell survival is highlighted, alongside the potential for targeting these pathways therapeutically. The review then summarizes previous work on nanoparticles for drug delivery and their advantages in cancer treatment over conventional methods.

This is a review article; therefore, it does not involve original research or data collection. The authors systematically reviewed existing literature on nanomaterials targeting cancer metabolic pathways. The search strategy likely included databases like PubMed, Web of Science, and others. Inclusion and exclusion criteria were used to select relevant studies. The selected studies were analyzed to identify key findings on different nanomaterials and their mechanisms of action against various cancer metabolic pathways. The findings are presented and discussed thematically, categorized by the metabolic pathway targeted (glucose, glutamine, lipid, acetate, etc.) and therapeutic approach (photothermal therapy, chemodynamic therapy, etc.). The review synthesized information from preclinical and clinical studies on various nanoparticles (lipids, polymers, metals, etc.) for cancer therapy and discusses their advantages, limitations, and potential for future development.

The review highlights the efficacy of nanoparticles (NPs) in targeting cancer metabolism. NPs offer advantages in drug delivery, including controlled release, enhanced solubility, and reduced toxicity to healthy cells. Passive and active targeting strategies using NPs are discussed. Specific examples of successful NPs-based cancer therapies include Genexol PM® (a nanoformulated paclitaxel) and verteporfin-loaded solid-lipid nanoparticles. The review extensively covers the application of various NPs (e.g., carbon dots, iron oxide particles, ruthenium sulfide nanoclusters, gold nanoparticles) in different cancer therapies (photothermal therapy, photodynamic therapy, hyperthermia). The unique properties of NPs such as high surface-to-volume ratio, magnetic behavior, and fluorescence are leveraged for targeted drug delivery and improved therapeutic efficacy. Targeting specific metabolic pathways is a key focus, with examples such as inhibiting polo-like kinase 1 (PLK1) using black phosphorus nanomaterials, and modifying glucose metabolism using mannose or inhibiting pyruvate dehydrogenase kinase 1 (PDK1) in endometrial carcinoma. The paper addresses metabolic heterogeneity within tumors, demonstrating the need for combination therapies targeting both proliferating and hypoxic cells. Examples of combination therapies targeting glucose and glutamine metabolism are presented. Finally, the role of oxidative stress and reactive oxygen species (ROS) in cancer is discussed, along with the therapeutic potential of ROS-generating NPs like silver nanoparticles and gold nanoparticles. The efficacy of combining photodynamic therapy (PDT) and chemodynamic therapy (CDT) is highlighted.

The findings demonstrate the significant potential of nanomaterials in revolutionizing cancer treatment by specifically targeting metabolic vulnerabilities of cancer cells. The review highlights how NPs overcome limitations of traditional therapies by enhancing drug delivery, improving specificity, and reducing side effects. The success of several NP-based therapies in preclinical and clinical trials underscores their efficacy. However, challenges remain such as toxicity, the mononuclear phagocytic system (MPS) uptake, and study design limitations when translating findings from in vitro and animal models to human trials. Addressing metabolic heterogeneity and the unique features of diverse cancer types require further research into tailored combination therapies. The integration of nanotechnology with immunotherapy shows promise for a more comprehensive approach.

Nanoparticle-based therapies show great promise in targeting cancer metabolism, offering enhanced efficacy and reduced side effects compared to conventional treatments. While challenges regarding toxicity and clinical translation remain, ongoing research and development of innovative nanomaterials and targeted therapies hold immense potential for improving cancer treatment outcomes. Future studies should focus on addressing heterogeneity and optimizing NP design for improved biocompatibility and targeting.

The review is based on existing literature and may not encompass all relevant studies. The generalization of findings from preclinical and small clinical trials to broader populations requires caution. The long-term effects of some nanoparticles and the impact of metabolic heterogeneity remain incompletely understood and require further investigation.