Evaluation and management of hypoactive sexual desire disorder in women. Recommendations from the 5th International Consultation on Sexual Medicine (ICSM 2024)

Tami S. Rowen

doi:10.1093/sxmrev/qeaf057

Hydroxylated poly(amidoamine) dendrimers mediate the co-delivery of proteins and drugs for enhanced neuroprotection against ischemic stroke

2026-08-11

0

PRE

AI

S

Siqi Geng

C

Caiyun Zhang

Z

Zhiqiang Wang

M

Mengyao Cui

D

Dzmitry Shcharbin *

M

Mingwu Shen

史向阳 (Xiangyang Shi) *

DOI：10.1016/j.actbio.2026.08.016

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Abstract

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Development of nanomedicines that can cross blood-brain barrier (BBB) for effective multi-target mitigation of ischemic stroke (IS) is still challenging. Here, we report a hydroxylated poly(amidoamine) dendrimer-based delivery system co-loaded with the immunomodulator fibronectin (FN) protein and the antioxidant neuroprotective drug edaravone (EDV) to tackle IS. We show that generation 5 (G5) poly(amidoamine) dendrimers partially functionalized with phenylboronic acid (PBA) and fully terminated with glycidol hydroxyl groups are able to co-load FN/EDV to form G5.N(Gly)OH-PBA/FN/EDV (GOPFE) nanocomplexes (NCs). The GOPFE exhibits a uniform particle size of 122.2 nm, satisfactory colloidal stability, pH/reactive oxygen species (ROS) dual-sensitive drug release behavior and favorable cytocompatibility. Benefiting from FN-mediated active targeting, the GOPFE can be efficiently internalized by microglia and neuronal cells and can cross BBB to selectively accumulate in cerebral inflammatory lesion due to the abundant dendrimer terminal hydroxyl groups and the FN-derived targeting capability. Mechanistically, the GOPFE effectively suppresses oxygen-glucose deprivation-triggered ROS overproduction, restrains excessive neuroinflammation, and ultimately alleviates neuronal apoptosis. In an IS rat model, the GOPFE preferentially accumulates in ischemic lesion, markedly reduces cerebral infarct volume, facilitates neurological functional recovery, and ameliorates ischemic BBB damage via FN-mediated angiogenesis effect. Moreover, the GOPFE orchestrates inflammatory and immune homeostasis, mitigates neuroinflammatory cascades, and attenuates neuronal damage, thereby executing comprehensive multi-target neuroprotection. Hence, the developed GOPFE NCs may hold a great promise as a targeted therapeutic nanomedicine for IS and other inflammation-related cerebrovascular diseases.

Keywords:

Poly(amidoamine) dendrimers

ischemic stroke

antioxidation

neuroprotection

revascularization

Hydroxylated poly(amidoamine) dendrimers mediate the co-delivery of proteins and drugs for enhanced neuroprotection against ischemic stroke

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