Is it time to rethink the Alzheimer's disease drug development strategy by targeting its silent phase?

Alzheimer＇s disease （AD） is the most frequent cause of dementia in the western world. In clinical terms, AD is characterized by progres- sive cognitive decline that usually begins with memory impairment. As the disease progresses, AD inevitably affects all intellectual functions including executive functions, leading to complete dependence for basic activities of daily life and premature death.

Improving cancer therapy by combining cell biological, physical, and molecular targeting strategies

Successful cancer therapy depends on selective killing of tumor cells while sparing normal cells. Selectivity can be achieved through treatment strategies that target tumor cells. A recent report from the Li laboratory （1） describes an elegant strategy to selectively kill tumor cells by combining several targeting strategies based on cell biological, physical, and molecular （genetic） properties of tumor and normal cells that enhances tumor cell killing in vitro and in an in vivo tumor xenograft model. The idea of using a multiplex targeting approach is reminiscent of strategies in which several antibiotics are used to treat bacterial infections while minimizing the chance that rare antibiotic-resistant mutants will arise within a population.

The inositol metabolism pathway as a target for neuroprotective strategies

Neurodegeneration is characterized by the progressive and permanent loss of neurons.Degeneration typically results in a debilitating loss of function in an otherwise healthy person.Neurodegenerative diseases have enormous direct health care costs,with some estimates for diseases.

Molecular neuro-oncology and development of targeted therapeutic strategies for brain tumors

Brain tumors are a diverse group of malignancies that remain refractory to conventional treatment approaches.Molecular neuro-oncologyhas now begun to clarify the transformed phenotype of brain tumors and identify oncogenic pathways that might be amenable to targetedtherapy.Activity of the phosphoinositide 3;kinase(PI3K)/Akt pathway is often upregulated in brain tumors due to excessive stimu-lation by growth factor receptors and Ras.Loss of function of the tumor suppressor gene PTEN also frequently contributesto

Nanomedicine for acute respiratory distress syndrome: The latest application, targeting strategy, and rational design

Acute respiratory distress syndrome(ARDS)is characterized by the severe inflammation and destruction of the lung aireblood barrier,leading to irreversible and substantial respiratory function damage.Patients with coronavirus disease 2019(COVID-19)have been encountered with a high risk of ARDS,underscoring the urgency for exploiting effective therapy.However,proper medications for ARDS are still lacking due to poor pharmacokinetics,non-specific side effects,inability to surmount pulmonary barrier,and inadequate management of heterogeneity.The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery.Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy,which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment.Through passive,active,or physicochemical targeting,nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment,thereby showing good therapeutic activity and reduced toxicity.This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy,highlights the strategies for targeted treatment of lung inflammation,presents the innovative drug delivery systems,and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.

Recent advances in drug delivery systems for targeting cancer stem cells

Cancer stem cells(CSCs)are a subpopulation of cancer cells with functions similar to those of normal stem cells.Although few in number,they are capable of self-renewal,unlimited proliferation,and multi-directional differentiation potential.In addition,CSCs have the ability to escape immune surveillance.Thus,they play an important role in the occurrence and development of tumors,and they are closely related to tumor invasion,metastasis,drug resistance,and recurrence after treatment.Therefore,specific targeting of CSCs may improve the efficiency of cancer therapy.A series of corresponding promising therapeutic strategies based on CSC targeting,such as the targeting of CSC niche,CSC signaling pathways,and CSC mitochondria,are currently under development.Given the rapid progression in this field and nanotechnology,drug delivery systems(DDSs)for CSC targeting are increasingly being developed.In this review,we summarize the advances in CSC-targeted DDSs.Furthermore,we highlight the latest developmental trends through the main line of CSC occurrence and development process;some considerations about the rationale,advantages,and limitations of different DDSs for CSCtargeted therapies were discussed.

Rational distribution of Ru nanodots on 2D Ti_(3−x)C_(2)T_(y)/g-C_(3)N_(4)heterostructures for boosted photocatalytic H_(2)evolution

Incorporating metal nanodots(NDs)into heterostructures for high charge separation and transfer capacities is one of the most effective strategies for improving their photocatalytic activities.However,controlling the space distribution of metal NDs for optimizing charge transport pathways remains a significant challenge,particularly in two-dimensional(2D)face-to-face heterostructures.Herein,we develop a simple targeted self-reduction strategy for selectively loading Ru NDs onto the Ti_(3−x)C_(2)T_(y)(TC)surface of 2D TC/g-C_(3)N_(4)(CN)heterojunction based on the reductive Ti vacancy defects creatively increased during the preparation of TC/CN by reducing calcination.Notably,the optimized Ru/TC/CN photocatalyst exhibits an outstanding H_(2)evolution rate of 3.21 mmol·g^(−1)·h^(−1)and a high apparent quantum efficiency of 30.9%at 380 nm,which is contributed by the unidirectional transfer of the photogenerated electrons from CN to Ru active sites(CN→TC→Ru)and the suppressed backflow of electrons from Ru sites to CN,as revealed by comprehensive characterizations and density functional theory(DFT)calculations.This work provides a novel strategy for synthesizing the highly efficient photocatalysts with a controllable charge transfer paths,which will boost the development of photocatalysis.

Aggregation-induced emission luminogens for in vivo molecular imaging and theranostics in cancer

Cancer is one of the most fatal diseases for decades.Aggregation-induced emission luminogens(AIEgens)have been recently used as molecular imaging or therapeutic agents in cancers,due to the advantages of large Stokes shift,high quantum yield,great biocompatibility,and strong photostability.AIEgens can specifically target different types of cancer via diverse targeting strategies.AIEgen-based fluorescence imaging,especially near-infrared imaging,demonstrated deep penetration and suitable signal-to-noise ratio,which allows reliable in vivo cancer imaging.Combined with other imaging modalities,AIEgen-based multimodal imaging could provide multidimensional cancer hallmarks from different perspectives.In addition,AIEgenbased phototherapy can be used for photodynamic therapy and photothermal therapy,which facilitate ablation of cancer cells with good biosafety and high therapeutic effects in vivo.AIEgens nanoparticles fabricated with some specific chemicals,drugs,or siRNA,could display synergistic therapeutic effects for cancers.This paper comprehensively describes the current status and future perspectives of AIEgens,which have showed a great potential for the future preclinical and clinical translation on in vivo molecular imaging and theranostics in cancer.