title: Blood-Brain-Barrier-Penetrating Albumin Nanoparticles for Biomimetic Drug Delivery via Albumin-Binding Protein Pathways for Antiglioma Therapy.
abstract: Nutrient transporters have been explored for biomimetic delivery targeting the brain. The albumin-binding proteins (e.g., SPARC and gp60) are overexpressed in many tumors for transport of albumin as an amino acid and an energy source for fast-growing cancer cells. However, their application in brain delivery has rarely been investigated. In this work, SPARC and gp60 overexpression was found on glioma and tumor vessel endothelium; therefore, such pathways were explored for use in brain-targeting biomimetic delivery. We developed a green method for blood-brain barrier (BBB)-penetrating albumin nanoparticle synthesis, with the capacity to coencapsulate different drugs and no need for cross-linkers. The hydrophobic drugs (i.e., paclitaxel and fenretinide) yield synergistic effects to induce albumin self-assembly, forming dual drug-loaded nanoparticles. The albumin nanoparticles can penetrate the BBB and target glioma cells via the mechanisms of SPARC- and gp60-mediated biomimetic transport. Importantly, by modification with the cell-penetrating peptide LMWP, the albumin nanoparticles display enhanced BBB penetration, intratumoral infiltration, and cellular uptake. The LMWP-modified nanoparticles exhibited improved treatment outcomes in both subcutaneous and intracranial glioma models, with reduced toxic side effects. The therapeutic mechanisms were associated with induction of apoptosis, antiangiogenesis, and tumor immune microenvironment regulation. It provides a facile method for dual drug-loaded albumin nanoparticle preparation and a promising avenue for biomimetic delivery targeting the brain tumor based on combination therapy.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.|Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University , Tianjin 300070, China.|Department of Pharmacy, Binzhou Medical University Hospital , 661 Huanghe Road, Binzhou 256603, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Lin
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.|Nanchang University College of Pharmacy , 461 Bayi Road, Nanchang 330006, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.
authors.forename: Yisi
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Jin
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University , Tianjin 300070, China.
authors.forename: Huining
authors.initials: H
authors.lastname: He
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University , Tianjin 300070, China.|University of Michigan College of Pharmacy , 428 Church Street, Ann Arbor, Michigan 48108, United States.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences , 501 Haike Road, Shanghai 201203, China.
authors.forename: Yongzhuo
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000418:Albumins / Q000737:chemistry*; D000818:Animals; D032701:Biomimetics; D001921:Brain; D001932:Brain Neoplasms / Q000188:drug therapy*; D002352:Carrier Proteins; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy*; D008807:Mice, Inbred BALB C; D053758:Nanoparticles
chemical_list: D000418:Albumins; D002352:Carrier Proteins
keywords: SPARC; albumin nanoparticle; albumin-binding protein; biomimetic delivery; brain tumor targeting; cell-penetrating peptide; gp60