Polymer-based nanocarriers to transport therapeutic biomacromolecules across the blood-brain barrier

作者：Elena Romero‐Ben, Upashi Goswami, Jackeline Soto-Cruz, Amirreza Mansoori-Kermani, Dhiraj Mishra, Sergio Martín‐Saldaña, Jone M. Ugartemendia, Alejandro Sosnik, Marcelo Calderón, Ana Beloqui, Aitor Larrañaga · 发表于：Acta Biomaterialia · 年份：2025 · DOI：10.1016/j.actbio.2025.02.065 · 被引用次数：32 · 研究领域：Nanoparticle-Based Drug Delivery、Advanced Drug Delivery Systems、Polymer Surface Interaction Studies

Therapeutic biomacromolecules such as genetic material, antibodies, growth factors and enzymes represent a novel therapeutic alternative for neurological diseases and disorders. In comparison to traditional therapeutics, which are mainly based on small molecular weight drugs that address the symptoms of these disorders, therapeutic biomacromolecules can reduce undesired side effects and target specific pathological pathways, thus paving the way towards personalized medicine. However, these biomacromolecules undergo degradation/denaturation processes in the physiological environment and show poor capacity to cross the blood-brain barrier (BBB). Consequently, they rarely reach the central nervous system (CNS) in their active form. Herein, we critically overview several polymeric nanocarriers that can protect and deliver therapeutic biomacromolecules across the BBB. Polymeric nanocarriers are first categorized based on their architecture (biodegradable solid nanoparticles, nanogels, dendrimers, self-assembled nanoparticles) that ultimately determines their physico-chemical properties and function. The available polymeric formulations are then thoroughly analyzed, placing particular attention on those strategies that ensure the stability of the biomacromolecules during their encapsulation process and promote their passage across the BBB by controlling their physical (e.g., mechanical properties, size, surface charge) and chemical (e.g., surface functional groups, targeting motifs...