Cancer Bioenergetics and Tumor Microenvironments—Enhancing Chemotherapeutics and Targeting Resistant Niches through Nanosystems

Abstract

Cancer is an impending bottleneck in the advanced scientific workflow to achieve diagnostic, prognostic, and therapeutic success. Most cancers are refractory to conventional diagnostic and chemotherapeutics due to their limited targetability, specificity, solubility, and side effects. The inherent ability of each cancer to evolve through various genetic and epigenetic transformations and metabolic reprogramming underlies therapeutic limitations. Though tumor microenvironments (TMEs) are quite well understood in some cancers, each microenvironment differs from the other in internal perturbations and metabolic skew thereby impeding the development of appropriate diagnostics, drugs, vaccines, and therapies. Cancer associated bioenergetics modulations regulate TME, angiogenesis, immune evasion, generation of resistant niches and tumor progression, and a thorough understanding is crucial to the development of metabolic therapies. However, this remains a missing element in cancer theranostics, necessitating the development of modalities that can be adapted for targetability, diagnostics and therapeutics. In this challenging scenario, nanomaterials are modular platforms for understanding TME and achieving successful theranostics. Several nanoscale particles have been successfully researched in animal models, quite a few have reached clinical trials, and some have achieved clinical success. Nanoparticles exhibit an intrinsic capability to interact with diverse biomolecules and modulate their functions. Furthermore, nanoparticles can be functionalized with receptors, modulators, and drugs to facilitate specific targeting with reduced toxicity. This review discusses the current understanding of different theranostic nanosystems, their synthesis, functionalization, and targetability for therapeutic modulation of bioenergetics, and metabolic reprogramming of the cancer microenvironment. We highlight the potential of nanosystems for enhanced chemotherapeutic success emphasizing the questions that remain unanswered.

Mitochondrial–Stem Cell Connection: Providing Additional Explanations for Understanding Cancer

“…The end-product of the glutaminolysis pathway is succinate (see Figure 4), which also contributes to extracellular acidification [185,186]. Furthermore, hyperosmolarity contributes to pH acidification by increasing extracellular Na+ concentration levels, which promotes aerobic glycolysis and leads to lactate accumulation [180,187,188]. Lactagenesis is a highly orchestrated effort that contributes to glycolysis, glutaminolysis, lactate production, a decrease of mitochondrial functions, angiogenesis, immunosuppression, cell migration, and metastases [185,189,190].…”

Repurposing mitochondrial-targeting anthelmintic agents with GLUT1 inhibitor BAY-876 for cancer therapy

“…[9][10][11][12] Recent literature has demonstrated that mitochondria remain functional even in cases where aerobic glycolysis is occurring as a means to offer biosynthetic intermediates to anabolic-proliferating cells while serving as sources of bioenergetics to cells in oxygenated environments. [13][14][15] Thus, targeting both glycolysis and mitochondrial respiration may provide a more durable treatment strategy when compared to targeting a single pathway.…”

Gold Nanoparticles Downregulate IL-6 Expression/Production by Upregulating microRNA-26a-5p and Deactivating the RelA and NF-κBp50 Transcription Pathways in Activated Breast Cancer Cells

“…Furthermore, GNP can be utilized in photothermal therapy, where they convert absorbed light energy into heat, selectively ablating cancer cells while sparing healthy tissue [43,44]. With ongoing research and advancements, gold nanoparticles hold great potential as therapeutics and imaging agents in a wide range of medical applications, offering opportunities for personalized and precise treatments in the future [45,46]. In this study, we proposed, for the first time, that GNP have the ability to suppress the over-secretion of IL-6 through modulation mediated by miRNAs.…”