Abstract:Novel agents are needed to improve chemoradiotherapy for locally advanced rectal cancer. In this study, we assessed the ability of CRLX101, an investigational nanoparticle-drug conjugate containing the payload camptothecin (CPT), to improve therapeutic responses as compared to standard chemotherapy. CRLX101 was evaluated as a radiosensitizer in colorectal cancer cell lines and murine xenograft models. CRLX101 was as potent as CPT in vitro in its ability to radiosensitize cancer cells. Evaluations in vivo demon… Show more
“…Therefore, novel anticancer strategies should include immunomodulatory approaches to subvert the tolerance to Nevertheless, a deep understanding of the tumor microenvironment is obligatory to overcome the related obstacles, as the entry and retention of NPs into the tumors, their fate and functionality as well as the challenging clinical translation in humans due to individual differences among patients, and tumors' heterogeneity [46]. Currently, most of the nanostrategies to enhance radiotherapeutic effects relies on the combination with chemotherapeutic agents [47,48], with several clinical trials ongoing [49]; anti-vascular agents [50]; radiosensitizers such as camptothecin [51], DNA repair inhibitors [52] and Pi3K inhibitors [53], which are generally very toxic when delivered systemically in their free forms. Also, the use of inorganic NPs as radiosensitizers has been extensively reported [54,55], despite remaining a challenge for clinical translation.…”
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
“…Therefore, novel anticancer strategies should include immunomodulatory approaches to subvert the tolerance to Nevertheless, a deep understanding of the tumor microenvironment is obligatory to overcome the related obstacles, as the entry and retention of NPs into the tumors, their fate and functionality as well as the challenging clinical translation in humans due to individual differences among patients, and tumors' heterogeneity [46]. Currently, most of the nanostrategies to enhance radiotherapeutic effects relies on the combination with chemotherapeutic agents [47,48], with several clinical trials ongoing [49]; anti-vascular agents [50]; radiosensitizers such as camptothecin [51], DNA repair inhibitors [52] and Pi3K inhibitors [53], which are generally very toxic when delivered systemically in their free forms. Also, the use of inorganic NPs as radiosensitizers has been extensively reported [54,55], despite remaining a challenge for clinical translation.…”
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
“…Up to now, various kinds of nanoparticles formulation of radiosensitive drugs for increasing the efficacy of RT have been designed . For example, based on the effective radiosensitization effect of chemodrug CDDP, Fan et al designed rattle‐structured multifunctional upconversion core/porous silica shell nanotheranostics (UCSNs) to deliver CDDP into tumor cells for achieving chemotherapy/RT synergetic treatment .…”
Section: General Strategies Of Nanomaterial‐mediated Tumor Radiosensimentioning
Nano-radiosensitization has been a hot concept for the past ten years, and the nanomaterial-mediated tumor radiosensitization method is mainly focused on increasing intracellular radiation deposition by high atomic number (high Z) nanomaterials, particularly gold (Au)-mediated radiation enhancement. Recently, various new nanomaterial-mediated radiosensitive approaches have been successively reported, such as catalyzing reactive oxygen species (ROS) generation, consuming intracellular reduced glutathione (GSH), overcoming tumor hypoxia, and various synergistic radiotherapy ways. These strategies may open a new avenue for enhancing the radiotherapeutic effect and avoiding its side effects. Nevertheless, reviews systematically summarizing these newly emerging methods and their radiosensitive mechanisms are still rare. Therefore, the general strategies of nanomaterial-mediated tumor radiosensitization are comprehensively summarized, particularly aiming at introducing the emerging radiosensitive methods. The strategies are divided into three general parts. First, methods on account of the intrinsic radiosensitive properties of nanoradiosensitizers for radiosensitization are highlighted. Then, newly developed synergistic strategies based on multifunctional nanomaterials for enhancing radiotherapy efficacy are emphasized. Third, nanomaterial-mediated radioprotection approaches for increasing the radiotherapeutic ratio are discussed. Importantly, the clinical translation of nanomaterial-mediated tumor radiosensitization is also covered. Finally, further challenges and outlooks in this field are discussed.
“…A series of polymer NPs can be used as drug carriers to enhance the radiosensitization effect by promoting DNA damage. Polymeric NPs containing camptothecin (CRLX101, 20-30 nm) promoted the formation and persistence of radiation-induced DSBs and inhibited radiation-induced HIF1α activation, which resulted in enhanced radiosensitization of HT-29 cells and xenograft models [101]. Irradiation can induce site-specific expression of receptors in tumor cells, such as tax-interaction protein 1 (TIP-1).…”
Section: Nanoradiosensitizers Based On Dna Damagementioning
Radiotherapy (RT) has been widely used for cancer treatment. However, the intrinsic drawbacks of RT, such as radiotoxicity in normal tissues and tumor radioresistance, promoted the development of radiosensitizers. To date, various kinds of nanoparticles have been found to act as radiosensitizers in cancer radiotherapy. This review focuses on the current state of nanoradiosensitizers, especially the related biological mechanisms, and the key design strategies for generating nanoradiosensitizers. The regulation of oxidative stress, DNA damage, the cell cycle, autophagy and apoptosis by nanoradiosensitizers in vitro and in vivo is highlighted, which may guide the rational design of therapeutics for tumor radiosensitization.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.