From molecular pathways to nanocarrier design: a translational framework for lipid-based nanoparticles in Alzheimer’s disease

@article{manna2026from,
  title = {{From molecular pathways to nanocarrier design: a translational framework for lipid-based nanoparticles in Alzheimer’s disease}},
  author = {Priya Manna and Aditi Maity and Suman Roy and Sayandeep Sahu and Souvik Pradhan and Shayeri Chatterjee Ganguly and Mainak Chakraborty and Moumita Kundu},
  journal = {Discover Nano},
  year = {2026},
  month = nov,
  doi = {10.1186/s11671-026-05124-1},
  url = {https://doi.org/10.1186/s11671-026-05124-1},
  note = {CC BY-NC-ND 4.0},
}

TY  - JOUR
TI  - From molecular pathways to nanocarrier design: a translational framework for lipid-based nanoparticles in Alzheimer’s disease
AU  - Priya Manna
AU  - Aditi Maity
AU  - Suman Roy
AU  - Sayandeep Sahu
AU  - Souvik Pradhan
AU  - Shayeri Chatterjee Ganguly
AU  - Mainak Chakraborty
AU  - Moumita Kundu
PY  - 2026
DA  - 2026/11/04
JO  - Discover Nano
DO  - 10.1186/s11671-026-05124-1
UR  - https://doi.org/10.1186/s11671-026-05124-1
AB  - Alzheimer’s disease, being a complicated neurodegenerative disoder affects cognitive as well as memory functions. Characterised by amyloid-β aggregation, along with tau hyperphosphorylation, and cholinergic dysfunction, this disease is also associated with oxidative stress and neuroinflammation. Conventional clinical interventions, like acetylcholinesterase inhibitors and novel monoclonal antibodies predominantly rely on symptomatic alleviation of symptoms. Nevertheless, these conventional treatments come across considerable constraints, like temporary effectiveness, lesser therapeutic reach due to the blood brain barrier, apart from additional adverse effects. To overcome these delivery obstacles and achieve intracellular targeting, lipid nanoparticles, such as liposomes, solid lipid nanoparticles, and drugs, that can effectively traverse biological barriers, and facilitate precise intracellular release. This review introduces a translational, pathway-integrated framework that connects key molecular mechanisms of the disease with rational design strategies of lipid nanocarriers. The review also illustrates how essential internal factors, such as lipid composition, ionizable lipid pKa, selection of helper lipids, PEG density, along with methods of endosomal escape, and the protein corona, affect brain targeting efficacy and toxicity. It further focuses on pathway-enforced nano lipidic therapeutic approaches, where nanocarrier design is tailored to cater to specific biological targets. Nano lipidic delivery of siRNA, miRNA, mRNA, monoclonal antibodies, and along with other neuroprotective agents has been emphasised. Additionally, advancements in surface functionalization, intranasal administration, as well as receptor-mediated transcytosis, and focused ultrasound-driven blood–brain barrier penetration have also been highlighted in this review. Therefore, it aims to bridge the gap between molecular pathology and formulation design through alignment of design principles that emphasize on nanocarrier properties and its relevance to disease-specific requirements, an approach that has never been comprehensively addressed in previous literature.  Registration number of clinical trial: Not applicable  Graphical abstract: Lipid nanoparticles carrying drugs, antibodies, or RNA are shown crossing the blood-brain barrier through transport receptors and escaping endosomes. Proposed therapeutic targets include amyloid beta aggregation, tau hyperphosphorylation, cholinergic dysfunction, oxidative stress, and neuroinflammation. The figure lists improved cognitive function, reduced pathology, and precision medicine as potential impacts.
SN  - 2731-9229
ER  -