Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and exhibits high rate of chemoresistance, metastasis, and relapse. This can be attributed to the failure of conventional therapeutics to target a sub-population of slow cycling or quiescent cells called as cancer stem cells (CSCs). Therefore, elimination of CSCs is essential for effective TNBC treatment.
Purpose: Research suggests that breast CSCs exhibit elevated glycolytic metabolism which directly contributes in maintenance of stemness, self-renewability and chemoresistance as well as in tumor progression. Therefore, this study aimed to target rewired metabolism which can serve as Achilles heel for CSCs population and have far reaching effect in TNBC treatment.
Methods: We used two preclinical models, zebrafish and nude mice to evaluate the fate of nanoparticles as well as the therapeutic efficacy of both piperlongumine (PL) and its nanomedicine (PL-NPs).
Results: In this context, we explored a phytochemical piperlongumine (PL) which has potent anti-cancer properties but poor pharmacokinetics impedes its clinical translation. So, we developed PLGA based nanomedicine for PL (PL-NPs), and demonstrated that it overcomes the pharmacokinetic limitations of PL, along with imparting advantages of selective tumor targeting through Enhanced Permeability and Retention (EPR) effect in zebrafish xenograft model. Further, we demonstrated that PL-NPs efficiently inhibit glycolysis in CSCs through inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) by modulating glutathione S-transferase pi 1 (GSTP1) and upregulation of fructose-1,6-bisphosphatase 1 (FBP1), a rate-limiting enzyme in gluconeogenesis. We also illustrated that inhibition of glycolysis results in overall tumor regression in two preclinical models.
Conclusion: This study discusses novel mechanism of action by which PL acts on CSCSs. Taken together our study provides insight into development of PL based nanomedicine which could be exploited in clinics to achieve complete eradication of TNBC by targeting CSCs.
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http://dx.doi.org/10.1016/j.phymed.2023.155181 | DOI Listing |
ACS Chem Biol
January 2025
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
As an important receptor in a host's immune and metabolic systems, NOD1 is usually activated by Gram-negative bacteria having -diaminopimelic acid (-DAP) in their peptidoglycan (PGN). But some atypical Gram-positive bacteria also contain -DAP in their PGN, giving them the potential to activate NOD1. The prevalence of -DAP-type Gram-positive bacteria in the gut, however, remains largely unknown.
View Article and Find Full Text PDFJ Mater Chem B
January 2025
Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Cardiovascular diseases (CVDs) are the foremost cause of mortality worldwide, with incidence and mortality rates persistently climbing despite extensive research efforts. Innovative therapeutic approaches are still needed to extend patients' lives and preserve their health. In the present study, novel supramolecular nanomedicine with both nitric oxide (NO) and antioxidant releasing ability was developed to enhance therapeutic efficacy against vascular injuries.
View Article and Find Full Text PDFTheranostics
January 2025
Department of Hepatopancreatobiliary Surgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, Hunan 421001, China.
Malignant tumors have been a serious threat to human health with their increasing incidence. Difficulties with conventional treatments are toxicity, drug resistance, and recurrence. For this reason, non-invasive treatment modalities such as photothermal therapy (PTT), photodynamic therapy (PDT), chemodynamic therapy (CDT), and others have received much attention.
View Article and Find Full Text PDFTheranostics
January 2025
School of Chemistry and Materials Science, Anhui Normal University, Wuhu 230022, China.
Reproductive health-related diseases have a significant impact on the well-being of millions of women worldwide, severely compromising their quality of life. Women encounter unique challenges in terms of reproductive health, including gynecological diseases and malignant neoplasms prior to pregnancy, as well as complications during pregnancy that greatly undermine their physical and mental health. Despite recent advancements in the field of female reproduction, substantial challenges still persist.
View Article and Find Full Text PDFTheranostics
January 2025
Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, 710061, China.
Gene therapy has evolved into a pivotal approach for treating genetic disorders, extending beyond traditional methods of directly repairing or replacing defective genes. Recent advancements in nucleic acid-based therapies-including mRNA, miRNA, siRNA, and DNA treatments have expanded the scope of gene therapy to include strategies that modulate protein expression and deliver functional genetic material without altering the genetic sequence itself. This review focuses on the innovative use of plant-derived nanovesicles (PDNVs) as a promising delivery system for these nucleic acids.
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