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Injectable Nanorobot-Hydrogel Superstructure for Hemostasis and Anticancer Therapy of Spinal Metastasis.

ABSTRACT: Surgery remains the standard treatment for spinal metastasis. However, uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes. In this study, we develop a thrombin (Thr)-loaded nanorobot-hydrogel hybrid superstructure by incorporating nanorobots into regenerated silk fibroin nanofibril hydrogels. This superstructure with superior thixotropic properties is injected percutaneously and dispersed into the spinal metastasis of hepatocellular carcinoma (HCC) with easy bleeding characteristics, before spinal surgery in a mouse model. Under near-infrared irradiation, the self-motile nanorobots penetrate into the deep spinal tumor, releasing Thr in a controlled manner. Thr-induced thrombosis effectively blocks the tumor vasculature and reduces bleeding, inhibiting tumor growth and postoperative recurrence with Au nanorod-mediated photothermal therapy. Our minimally invasive treatment platform provides a novel preoperative therapeutic strategy for HCC spinal metastasis effectively controlling intraoperative bleeding and tumor growth, with potentially reduced surgical complications and enhanced operative outcomes.

SUBMITTER: Chen Q

PROVIDER: S-EPMC11291792 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Injectable Nanorobot-Hydrogel Superstructure for Hemostasis and Anticancer Therapy of Spinal Metastasis.

Chen Qing Q Yan Miao M Hu Annan A Liang Bing B Lu Hongwei H Zhou Lei L Ma Yiqun Y Jia Chao C Su Dihan D Kong Biao B Hong Wei W Jiang Libo L Dong Jian J

Nano-micro letters 20240801 1

Surgery remains the standard treatment for spinal metastasis. However, uncontrolled intraoperative bleeding poses a significant challenge for adequate surgical resection and compromises surgical outcomes. In this study, we develop a thrombin (Thr)-loaded nanorobot-hydrogel hybrid superstructure by incorporating nanorobots into regenerated silk fibroin nanofibril hydrogels. This superstructure with superior thixotropic properties is injected percutaneously and dispersed into the spinal metastasis ...[more]

PMID: 39085736

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Project description:Immediately following spinal cord injury, further injury can occur through several secondary injury cascades. As a consequence of cell lysis, an increase in extracellular Ca(2+) results in additional neuronal loss by inducing apoptosis. Thus, hydrogels that reduce extracellular Ca(2+) concentration may reduce secondary injury severity. The goal of this study was to develop composite hydrogels consisting of alginate, chitosan, and genipin that interact with extracellular Ca(2+) to enable in situ gelation while maintaining an elastic modulus similar to native spinal cord (∼1000 Pa). It was hypothesized that incorporation of genipin and chitosan would regulate hydrogel electrostatic characteristics and influence hydrogel porosity, degradation, and astrocyte behavior. Hydrogel composition was varied to create hydrogels with statistically similar mechanical properties (∼1000 Pa) that demonstrated tunable charge characteristics (6-fold range in free amine concentration) and degradation rate (complete degradation between 7 and 28 days; some blends persist after 28 days). Hydrogels demonstrate high sensitivity to Ca(2+) concentration, as a 1 mM change during fabrication induced a significant change in elastic modulus. Additionally, hydrogels incubated in a Ca(2+)-containing solution exhibited an increased linear viscoelastic limit (LVE) and an increased elastic modulus above the LVE limit in a time dependent manner. An extension of the LVE limit implies a change in hydrogel cross-linking structure. Attachment assays demonstrated that addition of chitosan/genipin to alginate hydrogels induced up to a 4-fold increase in the number of attached astrocytes and facilitated astrocyte clustering on the hydrogel surface in a composition dependent manner. Furthermore, Western blots demonstrated tunable glial fibrillary acid protein (GFAP) expression in astrocytes cultured on hydrogel blends, with some hydrogel compositions demonstrating no significant increase in GFAP expression compared to astrocytes cultured on glass. Thus, alginate/chitosan/genipin hydrogel composites show promise as scaffolds that regulate astrocyte behavior and for the prevention of Ca(2+)-related secondary neuron damage during acute SCI.

Project description:BackgroundSpinal cord injury (SCI) is a serious injury with high mortality and disability rates, and there is no effective treatment at present. It has been reported that some treatments, such as drug intervention and stem cell transplantation have positive effects in promoting neurological recovery. Although those treatments are effective for nerve regeneration, many drawbacks, such as low stem cell survival rates and side effects caused by systemic medication, have limited their development. In recent years, injectable hydrogel materials have been widely used in tissue engineering due to their good biocompatibility, biodegradability, controllable properties, and low invasiveness. The treatment strategy of injectable hydrogels combined with stem cells or drugs has made some progress in SCI repair, showing the potential to overcome the drawbacks of traditional drugs and stem cell therapy.MethodsIn this study, a novel injectable electroactive hydrogel (NGP) based on sodium hyaluronate oxide (SAO) and polyaniline-grafted gelatine (NH2-Gel-PANI) was developed as a material in which to load neural stem cells (NSCs) and donepezil (DPL) to facilitate nerve regeneration after SCI. To evaluate the potential of the prepared NGP hydrogel in SCI repair applications, the surface morphology, self-repairing properties, electrical conductivity and cytocompatibility of the resulting hydrogel were analysed. Meanwhile, we evaluated the neural repair ability of NGP hydrogels loaded with DPL and NSCs using a rat model of spinal cord injury.ResultsThe NGP hydrogel has a suitable pore size, good biocompatibility, excellent conductivity, and injectable and self-repairing properties, and its degradation rate matches the repair cycle of spinal cord injury. In addition, DPL could be released continuously and slowly from the NGP hydrogel; thus, the NGP hydrogel could serve as an excellent carrier for drugs and cells. The results of in vitro cell experiments showed that the NGP hydrogel had good cytocompatibility and could significantly promote the neuronal differentiation and axon growth of NSCs, and loading the hydrogel with DPL could significantly enhance this effect. More importantly, the NGP hydrogel loaded with DPL showed a significant inhibitory effect on astrocytic differentiation of NSCs in vitro. Animal experiments showed that the combination of NGP hydrogel, DPL, and NSCs had the best therapeutic effect on the recovery of motor function and nerve conduction function in rats. NGP hydrogel loaded with NSCs and DPL not only significantly increased the myelin sheath area, number of new neurons and axon area but also minimized the area of the cystic cavity and glial scar and promoted neural circuit reconstruction.ConclusionsThe DPL- and NSC-laden electroactive hydrogel developed in this study is an ideal biomaterial for the treatment of traumatic spinal cord injury.

Dataset Information

Injectable Nanorobot-Hydrogel Superstructure for Hemostasis and Anticancer Therapy of Spinal Metastasis.

Publications

Injectable Nanorobot-Hydrogel Superstructure for Hemostasis and Anticancer Therapy of Spinal Metastasis.

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