Table 8.

Comparative classification of nano-immunomodulator platforms in AD and PD

Nanoparticle type	Targeting strategy	Therapeutic mechanism	Advantages	Limitations	References
Polydopamine nanoparticles	Intrinsic redox-active ROS scavenging; passive BBB interaction	Antioxidant and anti-inflammatory effects; suppression of pro-inflammatory signaling	Simple composition; broad mechanistic utility; intrinsic bioactivity	Batch variability; incomplete biodegradation profiling; limited clinical validation	Huang et al. (2026a), Ryu et al. (2018), Wang et al. (2026a), Duță et al. (2025), Duan et al. (2026), Ceccarelli et al. (2025), Wang et al. (2026b), Golchin et al. (2017)
Biomimetic nanozymes	Enzyme-mimetic catalytic activity; surface biomimicry	ROS neutralization; mitigation of mitochondrial stress and inflammasome priming	Multifunctional antioxidant capacity; may support mitophagy-related mechanisms	Composition-dependent reproducibility; uncertain long-term biodistribution; scale-up challenges	Chen et al. (2026), Godugu et al. (2025), Amniouel et al. (2025), Ma et al. (2025b), Xia et al. (2025), Zha et al. (2024)
Nanobody-based carriers	Ligand-mediated BBB traversal; disease-epitope targeting	Localized delivery of drugs or inhibitors to pathological CNS sites	High specificity; small size; reduced Fc-mediated effects	Rapid clearance; manufacturing complexity; limited in vivo durability	Lafon et al. (2025), Naeem et al. (2024), Tsitokana et al. (2023), Esparza et al. (2023), Jootar et al. (2026), Sun et al. (2025a)
Exosome-based nanocarriers	Natural vesicle tropism; surface engineering	Cargo delivery of miRNAs, siRNAs, small molecules, or proteins	High biocompatibility; native membrane properties; potential BBB crossing	Heterogeneity; low loading efficiency; standardization and regulatory constraints	Huang et al. (2026b), Onohuean et al. (2025), Évora et al. (2025), Feng et al. (2025), An et al. (2025), Shahlaei et al. (2025), Abdulkhaliq et al. (2026b), Kudpaje et al. (2025), Ke et al. (2026), Salarpour et al. (2025), Wang et al. (2024)
Nanotheranostics	Stimuli-responsive and imaging-guided targeting	Combined diagnosis and controlled release of therapeutic payloads	Real-time monitoring; localized delivery	Multi-component complexity; cost; uncertain long-term safety	Kochman et al. (2026), Zhao et al. (2025a), Sun et al. (2025b), Araujo et al. (2026), Prasanth et al. (2025), Ballance et al. (2019), Liu et al. (2026a), Zhang et al. (2023a), Zhang et al. (2023b), Guo et al. (2024b), Zhao et al. (2025b), Tian et al. (2025c)
Precision pathway interceptors	Disease-node targeting; multi-payload co-delivery	Simultaneous modulation of cGAS-STING, NLRP3, or A-related pathways	Mechanistically integrated design	Early preclinical status; regulatory complexity; limited validation	Xie et al. (2023), Chung et al. (2024), Hettiarachchi et al. (2019), Mitchell et al. (2021), Topal et al. (2020), Lin et al. (2025b), Ren et al. (2025), Younis et al. (2022)
Gene-delivering LNPs	Ligand-directed RNA delivery; endosomal escape optimization	Delivery of mRNA, siRNA, or CRISPR payloads to reprogram microglia	Modular; adaptable; strong mechanistic specificity	Delivery efficiency; off-target concerns; limited CNS clinical translation	Bai et al. (2025), Saber et al. (2024), Penney et al. (2024), Roamcharern and Yubolphan (2026)

Aβ Amyloid Beta, BBB Blood–Brain Barrier, cGAS Cyclic GMP-AMP Synthase, CRISPR Clustered Regularly Interspaced Short Palindromic Repeats, Fc Fragment crystallizable, LNPs Lipid Nanoparticles, miRNA(s) Micro Ribonucleic Acid(s), NLRP3 NOD-, LRR- and Pyrin Domain-Containing Protein 3, ROS Reactive Oxygen Species, siRNA(s): Small Interfering Ribonucleic Acid(s), STING Stimulator of Interferon Genes