Aug 2026· Advanced Healthcare Materials· pp.
e71545
· 0 citations· 129 references
Medicine
TL;DR
By moving beyond generic strategies for BBB penetration to address the distinctive pharmacotherapeutic shortcomings of depression, engineered nanomedicine holds great promise for advancing next-generation antidepressant therapies that achieve rapid onset, precise intervention, and comprehensive improvement in patient quality of life.
Abstract
Depression is a leading global health burden, yet current pharmacotherapy remains constrained by depression-specific challenges that extend beyond simple blood-brain barrier (BBB) penetration, including delayed onset of action, poor regional brain specificity, and the inability to deliver emerging biologics. Engineered nanomedicine offers a paradigm-shifting platform to address these limitations through precise designs such as receptor-mediated transport and cell-mimetic carriers, enabling targeted modulation of depression-related neural circuits. This review critically evaluates advanced nanoengineering strategies for antidepressant delivery, distinguishing proof-of-concept systems from platforms with realistic translational potential. We further provide a decision-oriented framework to guide future clinical development. By moving beyond generic strategies for BBB penetration to address the distinctive pharmacotherapeutic shortcomings of depression, engineered nanomedicine holds great promise for advancing next-generation antidepressant therapies that achieve rapid onset, precise intervention, and comprehensive improvement in patient quality of life.
This discussion aims to inspire a reorientation of nanomedicine strategies toward precision therapy for epilepsy by highlighting how emerging nanomedicines are expanding the therapeutic target repertoire to include key non-neuronal nodes, with a focus on neuroinflammation and BBB repair.
Yage Sun, Wenguang Liu· Journal of Controlled Releas...· 0 citations
The review proposes a three-step translational framework—patient stratification, target constraint, and cargo matching—and delineates five interlinked clinical development barriers: long-term safety of repeated BBB opening, technical standardization and reproducibility, quantifiable intracerebral PK, biological hit verification, and mechanism-enriched trial design.
Chungang Zhang, Deyu Fang, Lin Zhang· Drug Design, Development and...· 0 citations
This review systematically summarizes recent advances in nanomedicine enabled GBM therapy from four interrelated perspectives: the optimization of nanomaterial properties, the development of goal-oriented targeting strategies, the rationalization of delivery routes, and the engineering of smart stimuli-responsive nano-systems.
Yu Guo, Keqiang Lu, Wenmiao Luo et al.· Wiley Interdisciplinary Revi...· 1 citation
Active targeting in nanomedicine aims to enhance therapeutic efficacy by functionalising nanocarriers with ligands that selectively bind biological targets. Despite extensive research, clinical translation has remained limited, with most approved systems relying on antibodies or passive delivery mechanisms rather than complex targeted nanoparticles. This perspective critically examines the gap between the conceptual promise of active targeting and its practical performance. Drawing comparisons with biological systems, we highlight that natural targeting relies on dynamic, multi‐step and energy‐dependent processes rather than simple ligand–receptor interactions. Current nanomedicine approaches are constrained by an oversimplified view of targeting, neglecting key factors such as multivalency, spatial organisation, kinetics and biological barriers. Future progress requires a shift towards systems‐level design, integrating spatiotemporal control, adaptive materials and computational modelling. Ultimately, we propose a design‐by‐architecture paradigm, in which targeting is encoded into nanomaterial structure, enabling programmable and biologically guided delivery.
Cancer remains a major global health challenge, with conventional therapies limited by low specificity, systemic-toxicity, and drug resistance. Cancer nanomedicine has emerged as a transformative field, leveraging unique nanomaterial properties for advanced diagnostic and therapeutic applications. This review explores the preclinical advantages of nanotherapies, such as enhanced drug delivery and theranostic capabilities, and critically analyzes the bottlenecks impeding their clinical translation. This manuscript reviews the current landscape of cancer nanomedicine by comprehensively synthesizing findings from peer-reviewed literature across a number of academic databases. The methodology involved critically evaluating the efficacy and safety profiles of various nanotherapeutic approaches in preclinical settings. Concurrently, the systemic and biological impediments to their clinical translation were identified and analyzed, including challenges related to in-vivo delivery, immune interactions, manufacturing, and regulatory compliance. This synthesis identifies overarching trends and critical gaps in the understanding of nanomedicine's translational pathway. This review identified a consistent body of preclinical evidence highlighting significant advantages of cancer nanotherapies. This includes enhanced drug solubility and bioavailability, reduced systemic side effects, improved tumor targeting via the Enhanced Permeability and Retention (EPR) effect and active ligands, and the ability to overcome multidrug resistance. Concurrently, the review identified persistent, multifaceted bottlenecks to clinical translation. These include low tumor accumulation in-vivo, rapid immune clearance, tumor heterogeneity, unpredictable toxicity profiles, manufacturing scalability issues, and complex regulatory pathways. Coupled with difficulties in translating in-vitro results to in-vivo success, these emerged as critical impediments. The "translational gap" stems largely from discrepancies between uniform preclinical models and heterogeneous human tumors, rendering the EPR effect clinically unreliable. Consequently, the field must pivot from "one-size-fits-all" formulations toward precision medicine. This requires biomarker stratification to identify responsive patient populations and "Safe-by-Design" frameworks to address manufacturing and toxicity inconsistencies prior to clinical application. While nanotherapies offer transformative potential to overcome conventional treatment limitations, this review underscores critical gaps in clinical translation. Addressing these barriers requires interdisciplinary collaboration among academia, industry, and regulators. Advancements will hinge on cutting-edge nanotechnologies, deepening understanding of nano-biological interactions, and adopting "safe-by-design" principles. This evolution is crucial to accelerate nanodrugs from discovery to widespread clinical application.
David Beniameen, Ahmed Abdelghany· Undergraduate Research in Na...· 0 citations
Stroke remains a leading global health problem, and effective neuroprotective and regenerative therapies are still limited. Although acute-phase reperfusion strategies have advanced, their narrow therapeutic windows and the risk of reperfusion injury highlight the urgent need for broader neuroprotective and regenerative approaches. Here, we review lipid-based nanocarriers as a drug delivery platform, with a particular focus on spatiotemporal drug delivery across distinct stroke phases (acute, subacute, and recovery). To date, no dedicated review has comprehensively summarized the spatiotemporal applications of lipid-based nanocarriers in stroke therapy. We discuss their potential for blood-brain barrier (BBB) penetration, inflammation modulation, and neural regeneration. Despite these promising opportunities, substantial challenges remain, including standardized formulation and barriers to clinical translation. This review offers theoretical and practical guidance for future translational efforts, emphasizing chemical design of lipid-based carriers and its role in optimizing therapeutic efficacy.
Miaomiao Xiao, Nan Zhang, Qinghua Meng et al.· ACS Biomaterials Science & E...· 0 citations
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