Macrophage Membrane-Camouflaged Responsive Polymer Nanogels Enable Magnetic Resonance Imaging-Guided Chemotherapy/Chemodynamic Therapy of Orthotopic Glioma. Xiao Tingting,He Meijuan,Xu Fang,Fan Yu,Jia Bingyang,Shen Mingwu,Wang Han,Shi Xiangyang ACS nano Development of innovative nanomedicine formulations to traverse the blood-brain barrier (BBB) for effective theranostics of glioma remains a great challenge. Herein, we report the creation of macrophage membrane-camouflaged multifunctional polymer nanogels coloaded with manganese dioxide (MnO) and cisplatin for magnetic resonance (MR) imaging-guided chemotherapy/chemodynamic therapy (CDT) of orthotopic glioma. Redox-responsive poly(-vinylcaprolactam) (PVCL) nanogels (NGs) formed via precipitation polymerization were loaded with MnO and physically encapsulated with cisplatin to have a mean size of 106.3 nm and coated with macrophage membranes to have a good colloidal stability. The generated hybrid NGs display dual pH- and redox-responsive cisplatin and Mn(II) release profiles and can deplete glutathione (GSH) rich in tumor microenvironment through reaction with disulfide-containing cross-linkers within the NGs and MnO. The thus created Mn(II) enables enhanced CDT through a Fenton-like reaction and -weighted MR imaging, while the loaded cisplatin not only exerts its chemotherapy effect but also promotes the reactive oxygen species generation to enhance the CDT efficacy. Importantly, the macrophage membrane coating rendered the hybrid NGs with prolonged blood circulation time and ability to traverse BBB for specific targeted chemotherapy/CDT of orthotopic glioma. Our study demonstrates a promising self-adaptive and cooperative NG-based nanomedicine platform for highly efficient theranostics of glioma, which may be extended to tackle other difficult cancer types. 10.1021/acsnano.1c08689

A review on biomaterials for ovarian tissue engineering. Dadashzadeh Arezoo,Moghassemi Saeid,Shavandi Amin,Amorim Christiani A Acta biomaterialia Considerable challenges in engineering the female reproductive tissue are the follicle's unique architecture, the need to recapitulate the extracellular matrix, and tissue vascularization. Over the years, various strategies have been developed for preserving fertility in women diagnosed with cancer, such as embryo, oocyte, or ovarian tissue cryopreservation. While autotransplantation of cryopreserved ovarian tissue is a viable choice to restore fertility in prepubertal girls and women who need to begin chemo- or radiotherapy soon after the cancer diagnosis, it is not suitable for all patients due to the risk of having malignant cells present in the ovarian fragments in some types of cancer. Advances in tissue engineering such as 3D printing and ovary-on-a-chip technologies have the potential to be a translational strategy for precisely recapitulating normal tissue in terms of physical structure, vascularization, and molecular and cellular spatial distribution. This review first introduces the ovarian tissue structure, describes suitable properties of biomaterials for ovarian tissue engineering, and highlights recent advances in tissue engineering for developing an artificial ovary. STATEMENT OF SIGNIFICANCE: The increase of survival rates in young cancer patients has been accompanied by a rise in infertility/sterility in cancer survivors caused by the gonadotoxic effect of some chemotherapy regimens or radiotherapy. Such side-effect has a negative impact on these patients' quality of life as one of their main concerns is generating biologically related children. To aid female cancer patients, several research groups have been resorting to tissue engineering strategies to develop an artificial ovary. In this review, we discuss the numerous biomaterials cited in the literature that have been tested to encapsulate and in vitro culture or transplant isolated preantral follicles from human and different animal models. We also summarize the recent advances in tissue engineering that can potentially be optimal strategies for developing an artificial ovary. 10.1016/j.actbio.2021.08.026

A multi-modal delivery strategy for spinal cord regeneration using a composite hydrogel presenting biophysical and biochemical cues synergistically. Man Weitao,Yang Shuhui,Cao Zheng,Lu Jiaju,Kong Xiangdong,Sun Xiaodan,Zhao Lingyun,Guo Yi,Yao Shenglian,Wang Guihuai,Wang Xiumei Biomaterials Extensive tissue engineering studies have supported the enhanced spinal cord regeneration by implantable scaffolds loaded with bioactive cues. However, scaffolds with single-cue delivery showed unsatisfactory effects, most likely due to the complex nature of hostile niches in the lesion area. In this regard, strategies of multi-modal delivery of multiple heterogeneous cell-regulatory cues are unmet needs for enhancing spinal cord repair, which requires a thorough understanding of the regenerative niche associated with spinal cord injury. Here, by combining hierarchically aligned fibrin hydrogel (AFG) and functionalized self-assembling peptides (fSAP), a novel multifunctional nanofiber composite hydrogel AFG/fSAP characterized with interpenetrating network is designed. Serving as a source of both biophysical and biochemical cues, AFG/fSAP can facilitate spinal cord regeneration via guiding regenerated tissues, accelerating axonal regrowth and remyelination, and promoting angiogenesis. Giving the synergistic effect of multiple cues, AFG/fSAP implantation contributes to anatomical, electrophysiological, and motor functional restorations in rats with spinal cord hemisection. This study provides a novel multi-modal approach for regeneration in central nervous system, which has potentials for clinical practice of spinal cord injury. 10.1016/j.biomaterials.2021.120971

Nanotheranostics for the Management of Hepatic Ischemia-Reperfusion Injury. Guan Yu,Yao Weifeng,Yi Ke,Zheng Chunxiong,Lv Shixian,Tao Yu,Hei Ziqing,Li Mingqiang Small (Weinheim an der Bergstrasse, Germany) Hepatic ischemia-reperfusion injury (IRI), in which an insufficient oxygen supply followed by reperfusion leads to an inflammatory network and oxidative stress in disease tissue to cause cell death, always occurs after liver transplantations and sections. Although pharmacological treatments favorably prevent or protect the liver against experimental IRI, there have been few successes in clinical applications for patient benefits because of the incomprehension of complicated IRI-induced signaling events as well as short blood circulation time, poor solubility, and severe side reactions of most antioxidants and anti-inflammatory drugs. Nanomaterials can achieve targeted delivery and controllable release of contrast agents and therapeutic drugs in desired hepatic IRI regions for enhanced imaging sensitivity and improved therapeutic effects, emerging as novel alternative approaches for hepatic IRI diagnosis and therapy. In this review, the application of nanotechnology is summarized in the management of hepatic IRI, including nanomaterial-assisted hepatic IRI diagnosis, nanoparticulate systems-mediated remission of reactive oxygen species-induced tissue injury, and nanoparticle-based targeted drug delivery systems for the alleviation of IRI-related inflammation. The current challenges and future perspectives of these nanoenabled strategies for hepatic IRI treatment are also discussed. 10.1002/smll.202007727

A mitochondria-targeting magnetothermogenic nanozyme for magnet-induced synergistic cancer therapy. Biomaterials Magnetic hyperthermia therapy (MHT) and chemodynamic therapy (CDT) are non-invasive in situ treatments without depth limitations and with minimum adverse effects on surrounding healthy tissue. We herein report a mitochondria-targeting magnetothermogenic nanozyme (Ir@MnFeO NPs) for highly efficient cancer therapy. An iridium(III) complex (Ir) acts as a mitochondria-targeting agent on the surface of MnFeO NPs. On exposure to an alternating magnetic field (AMF), the Ir@MnFeO NPs induce a localized increase in temperature causing mitochondrial damage (MHT effect). Meanwhile glutathione (GSH) reduces Fe(III) to Fe(II) on the NPs surface, which in turn catalyzes the conversion of HO to cytotoxic •OH (CDT effect). The depletion of GSH (a •OH scavenger) increases CDT efficacy, while the localized increase in temperature increases the rate of conversion of both Fe(III) to Fe(II) and HO to •OH further enhancing the CDT effect. In addition, the disruption of cellular redox homeostasis due to CDT, leads to greater sensitivity of the cell towards MHT. This nanoplatform integrates these excellent therapeutic properties, with two-photon microscopy (TPM) (demonstrated in vitro) and magnetic resonance imaging (MRI) (demonstrated in vivo) to enable the precise and effective treatment of cancer. 10.1016/j.biomaterials.2020.120079