Amyloid-β/Tau burden and neuroinflammation dual-targeted nanomedicines synergistically restore memory and recognition of Alzheimer’s disease mice

Zhang, Lingxiao; Hou, Shengjie; Movahedi, Fatemeh; Li, Zijin; Li, Li; Hu, Jing; Jia, Yingbo; Huang, Yaru; Zhu, Jie; Sun, Xiaoying; Zeng, Ling‐Hui; Liu, Ruitian; Xu, Zhi Ping

doi:10.1016/j.nantod.2023.101788

Cited by 15 publications

(11 citation statements)

References 72 publications

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“…On this basis, the chemical drugs can also be replaced by other ligands such as angiopep-2 and rabies virus glycoprotein endow LDH with excellent tissue/cell targeting capability. 21,22 Meanwhile, cancer cell membrane-coating technology further enhances the tumortargeting ability of LDH through homologous homing, and our recent study showed a nearly 3-fold increase in tumor accumulation compared to BSA-coated one. 23 Notably, nanomedicines are easily diffused or metabolized from tumors, which has become another challenge to be addressed.…”

Section: Tumor-targeted Drug Deliverymentioning

confidence: 90%

“…The ICG/Cu-LDH@BSA-DOX nanomedicines efficiently released DOX in the acidic tumors and generated heat and reactive oxygen species (ROS) to synergistically induce skin cancer cell apoptosis upon mild 808 nm laser irradiation (0.3 W/cm 2 for 2 min) at very low drug doses (DOX = 0.175 mg/kg, Cu = 0.5 mg/kg, ICG = 0.25 mg/kg). On this basis, the chemical drugs can also be replaced by other ligands such as angiopep-2 and rabies virus glycoprotein endow LDH with excellent tissue/cell targeting capability. , Meanwhile, cancer cell membrane-coating technology further enhances the tumor-targeting ability of LDH through homologous homing, and our recent study showed a nearly 3-fold increase in tumor accumulation compared to BSA-coated one …”

Section: As Dds: Ldh Delivers Therapeutics Against Cancersmentioning

confidence: 93%

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Beyond Drug Delivery System: Immunomodulatory Layered Double Hydroxide Nanoadjuvants Take an Essential Step Forward in Cancer Immunotherapy

Zhu

Jiang²,

Jia³

et al. 2023

Acc. Mater. Res.

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Conspectus Layered double hydroxide (LDH) is an anionic two-dimensional plate-like nanomaterial consisting of positively charged divalent and trivalent cation layers and anion-exchangeable interlayer galleries alternatingly. In the past decades, LDH has been widely explored as a versatile drug delivery system (DDS) for delivering small molecules, genes, peptides, and proteins due to its excellent drug-loading capacity and feasible surface modification. At the cellular level, LDH can be easily internalized by cells, escape rapidly (<30 min) from endosomes/lysosomes, and subsequently diffuse into the cytoplasm and mitochondria, which provides an important basis for achieving subcellular organelle-targeted drug delivery. At the body level, LDH is able to actively target different organs by optimizing the physicochemical properties (e.g., size and colloidal stability) and surface modification. Beyond DDS, LDH has been used as an antacid drug Talcid for nearly half a century, and its chemical composition is also highly similar to commercial aluminum adjuvants; thus, LDH has been redefined as a new type of antacid nanoaluminum adjuvant for cancer immunotherapy. Notably, the flexible composition of LDH enables its metal cations and defect sites in the LDH layer to be tailored according to the needs of cancer immunotherapy. On the one hand, doping nutritional metal cations into LDH layers can greatly enhance the ability of LDH to activate immune cells and induce tumor immunogenic cell death, thereby improving its efficiency in inducing systemic immune responses. On the other hand, the modulation of defect sites in the crystal structure of LDH enables itself to sensitively respond to external stimuli for photothermal/photodynamic therapy, sonodynamic therapy, and pH-sensitive magnetic resonance imaging. Therefore, two-dimensional LDH nanomaterials with high physicochemical plasticity are emerging as drug-free or drug-minimal candidates for visualized cancer immunotherapy. In this Account, we briefly introduce the application of LDH as DDS in delivering small molecules, genes, peptides, proteins, and vaccines against malignant tumors, as well as the related surface modification strategies for enhancing LDH-based nanomedicine/vaccine accumulation in the targeted tissues. Then, we highlight our group’s work in preparing drug-free or drug-minimal LDH for efficient cancer immunotherapy beyond DDS. We are focusing on exploring the influence of the intrinsic physicochemical properties of LDH on its activation of the immune system, induction of tumor cell death, and evocation of protective antitumor immune responses. The perspectives associated with the application of immunomodulatory LDH for visualized cancer immunotherapy are also discussed. We envision that these drug-free or drug-minimal LDH nanomaterials for cancer immunotherapy will stimulate the development of simple and highly effective immunomodulatory nanomaterials to fight cancer.

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Section: Tumor-targeted Drug Deliverymentioning

confidence: 90%

Section: As Dds: Ldh Delivers Therapeutics Against Cancersmentioning

confidence: 93%

Beyond Drug Delivery System: Immunomodulatory Layered Double Hydroxide Nanoadjuvants Take an Essential Step Forward in Cancer Immunotherapy

Zhu

Jiang²,

Jia³

et al. 2023

Acc. Mater. Res.

Self Cite

View full text Add to dashboard Cite

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“…Intravenous LRsGAR injection significantly decreases GSK‐3β mRNA levels in the hippocampus and cortex of Tau.P301S AD mice, and ultimately decreases p‐Tau accumulation in the brain (Figure 3J,K). [119] …”

Section: Nanomedicines For Targeting Tauopathymentioning

confidence: 99%

“…P301S AD mice, and ultimately decreases p-Tau accumulation in the brain (Figure 3J,K). [119] In summary, several therapeutic strategies can attenuate tauopathy, including methods that reduce p-Tau expression, clear p-Tau, inhibit p-Tau aggregation and stabilize the cytoskeleton. Nanomedicines allow the precise adoption of the first three therapeutic strategies.…”

Section: Nanomedicines For Targeting Tauopathymentioning

confidence: 99%

Nanomedicines for Alzheimer's disease: Therapies based on pathological mechanisms

Cheng

Xie

Zhao

et al. 2023

Brain-X

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Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide. Because of the complex pathogenesis of AD and the unique location of AD lesions, effective clinical treatment strategies for this disease remain elusive. However, the development of nanotechnology has allowed a new era of AD treatment to emerge. AD nanomedicines are products of interdisciplinary research that enable high precision and targeted delivery. Additionally, they can specifically regulate various pathogenic factors. This review focuses on nanomedicines based on the pathological mechanisms of AD that can target AD lesions. We also discuss the precise regulatory effects of nanomedicines (including the nanomaterials themselves) on pathogenic proteins, neuroinflammatory molecules, and other pathogenic factors. We summarize the clinical trials that have examined new AD drugs, highlighting the development of new nanomedicines and the progress in their clinical translation. Nanotechnology‐based AD treatment is a nascent field, and a complete cure is distant at present; therefore, we also elaborate on the shortcomings of current AD nanomedicines. Finally, we discuss the prospects to guide the future development of AD nanomedicines.

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“…[ 58 ] The dual‐targeted LDH‐Rutin‐siRNA/Ang2‐RVG29, LRsAR (Table 1) silences BACE1 (for Aβ) or GSK3β (for p‐Tau) by absorbing gene silence module on the surface of magnesium/aluminium layered double hydroxide (LDH) nanoparticle. [ 59 ]…”

Section: Mechanism Of Alzheimer's Diseasementioning

confidence: 99%

Alzheimer's Disease: Status of Low‐Dimensional Nanotherapeutic Materials

Huang,

Liao,

et al. 2023

Adv Funct Materials

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Alzheimer's disease (AD) is a chronic progressive neurodegenerative disease that constitutes the third most common cause of death among elderly individuals. AD patients suffer from behavioral problems regularly, like memory loss, thinking deficits, and cognitive disorders. Currently, the incidence rate of AD has been on the rise worldwide. Therefore, it is imperative to develop effective strategies for the treatment and prevention of AD. The inherent characteristics of low‐dimensional nanomaterials, primarily their smaller size and surface structure, make them well‐suited for fulfilling the essential requirements of therapeutic drug design. Consequently, these nanomaterials offer a highly appealing and alternative approach to treating AD. Here, the low‐dimensional nanomaterials used in the treatment of AD to provide new ideas, methods, and comprehensive perspectives for the management of AD are reviewed. This review will advance the comprehensive understanding of the potential of low‐dimensional nanomaterials in the field of neuro medicine, which also will have a positive impact on future research.

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Amyloid-β/Tau burden and neuroinflammation dual-targeted nanomedicines synergistically restore memory and recognition of Alzheimer’s disease mice

Cited by 15 publications

References 72 publications

Beyond Drug Delivery System: Immunomodulatory Layered Double Hydroxide Nanoadjuvants Take an Essential Step Forward in Cancer Immunotherapy

Beyond Drug Delivery System: Immunomodulatory Layered Double Hydroxide Nanoadjuvants Take an Essential Step Forward in Cancer Immunotherapy

Nanomedicines for Alzheimer's disease: Therapies based on pathological mechanisms

Alzheimer's Disease: Status of Low‐Dimensional Nanotherapeutic Materials

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