Metabolomics is becoming a relevant tool for understanding the molecular mechanisms involved in the response to new drug delivery systems. The applicability of this experimental approach to cell cultures and animal models makes metabolomics a useful tool for establishing direct connections between in vitro and in vivo data, thus providing a reliable platform for the characterization of chemotherapeutic agents. Herein, we used metabolomic profiles based on nuclear magnetic resonance (NMR) spectroscopy to evaluate the biochemical pathways involved in the response to a chemotherapeutic anthracycline drug (Doxorubicin, Dox) and an N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-conjugated form (HPMA-Dox) in an in vitro cell culture model and an in vivo orthotopic breast cancer model. We also used protein expression and flow cytometry studies to obtain a better coverage of the biochemical alterations associated with the administration of these compounds. The overall analysis revealed that polymer conjugation leads to increased apoptosis, reduced glycolysis, and reduced levels of phospholipids when compared to the free chemotherapeutic drug. Our results represent a first step in the application of integrated in vitro and in vivo metabolomic studies to the evaluation of drug delivery systems.
Current prostate cancer (PCa) treatment options include hormonal therapy, chemotherapy, immunotherapy, and radiotherapy; however, a lack of targeting and overall efficiency has failed to improve survival rates or reduce unwanted side‐effects in advanced stage PCa patients. The modification of existing therapeutics, including their reformulation as nanomedicines, can increase stability in plasma, enhance tumor targeting, and improve pharmacokinetics to foster improvements in patient outcomes. This review now describes those nanomedicinal approaches to advanced PCa treatment under evaluation in both preclinical and clinical studies. Despite the current advantages provided by nanomedicine in PCa treatment, there exists the opportunity to improve the design of novel therapeutic approaches. Therefore, this review also highlights the importance of identifying novel functional biomarkers to stratify patients and guide nanomedicinal design. Finally, the authors describe strategies employed to enhance the passive accumulation of nanomedicines in tumors and discuss the enormous potential of combination therapies that target tumor cells and the all‐important tumor microenvironment to reduce tumor growth and overcome therapeutic resistance.
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