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      Stimuli-activatable nanomedicine meets cancer theranostics

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          Abstract

          Stimuli-activatable strategies prevail in the design of nanomedicine for cancer theranostics. Upon exposure to endogenous/exogenous stimuli, the stimuli-activatable nanomedicine could be self-assembled, disassembled, or functionally activated to improve its biosafety and diagnostic/therapeutic potency. A myriad of tumor-specific features, including a low pH, a high redox level, and overexpressed enzymes, along with exogenous physical stimulation sources (light, ultrasound, magnet, and radiation) have been considered for the design of stimuli-activatable nano-medicinal products. Recently, novel stimuli sources have been explored and elegant designs emerged for stimuli-activatable nanomedicine. In addition, multi-functional theranostic nanomedicine has been employed for imaging-guided or image-assisted antitumor therapy. In this review, we rationalize the development of theranostic nanomedicine for clinical pressing needs. Stimuli-activatable self-assembly, disassembly or functional activation approaches for developing theranostic nanomedicine to realize a better diagnostic/therapeutic efficacy are elaborated and state-of-the-art advances in their structural designs are detailed. A reflection, clinical status, and future perspectives in the stimuli-activatable nanomedicine are provided.

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          Dysregulated pH: a perfect storm for cancer progression.

          Although cancer is a diverse set of diseases, cancer cells share a number of adaptive hallmarks. Dysregulated pH is emerging as a hallmark of cancer because cancers show a 'reversed' pH gradient with a constitutively increased intracellular pH that is higher than the extracellular pH. This gradient enables cancer progression by promoting proliferation, the evasion of apoptosis, metabolic adaptation, migration and invasion. Several new advances, including an increased understanding of pH sensors, have provided insight into the molecular basis for pH-dependent cell behaviours that are relevant to cancer cell biology. We highlight the central role of pH sensors in cancer cell adaptations and suggest how dysregulated pH could be exploited to develop cancer-specific therapeutics.
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            Targeting the tumour stroma to improve cancer therapy

            Cancers are not composed merely of cancer cells alone; instead, they are complex 'ecosystems' comprising many different cell types and noncellular factors. The tumour stroma is a critical component of the tumour microenvironment, where it has crucial roles in tumour initiation, progression, and metastasis. Most anticancer therapies target cancer cells specifically, but the tumour stroma can promote the resistance of cancer cells to such therapies, eventually resulting in fatal disease. Therefore, novel treatment strategies should combine anticancer and antistromal agents. Herein, we provide an overview of the advances in understanding the complex cancer cell-tumour stroma interactions and discuss how this knowledge can result in more effective therapeutic strategies, which might ultimately improve patient outcomes.
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              Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy?

              Nissim Hay (2016)
              In recent years there has been a growing interest among cancer biologists in cancer metabolism. This Review summarizes past and recent advances in our understanding of the reprogramming of glucose metabolism in cancer cells, which is mediated by oncogenic drivers and by the undifferentiated character of cancer cells. The reprogrammed glucose metabolism in cancer cells is required to fulfil anabolic demands. This Review discusses the possibility of exploiting the reprogrammed glucose metabolism for therapeutic approaches that selectively target cancer cells.
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                Author and article information

                Journal
                Theranostics
                Theranostics
                thno
                Theranostics
                Ivyspring International Publisher (Sydney )
                1838-7640
                2023
                2 October 2023
                : 13
                : 15
                : 5386-5417
                Affiliations
                [1 ]Department of Radiology, and Department of Geriatrics, Laboratory of Heart Valve Disease, Huaxi MR Research Center (HMRRC), Laboratory of Stem Cell Biology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu 610041, China.
                [2 ]Functional and Molecular Imaging Key Laboratory of Sichuan Province and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China
                [3 ]Department of Radiology, West China Xiamen Hospital of Sichuan University, 699 Jinyuan Xi Road, Jimei District, 361021 Xiamen, Fujian, China.
                Author notes
                ✉ Corresponding author: E-mail: luokui@ 123456scu.edu.cn .

                *Those authors contributed equally to this work.

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                thnov13p5386
                10.7150/thno.87854
                10614691
                37908735
                1d3b4131-36e3-4ba9-803f-3a5d0db25bb4
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                History
                : 6 July 2023
                : 5 September 2023
                Categories
                Review

                Molecular medicine
                exogenous stimuli,endogenous stimuli,stimuli activation,nanomedicine,cancer theranostics

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