Drug-Induced Self-Assembly of Modified Albumins as Nano-theranostics for Tumor-Targeted Combination Therapy

• Published in: ACS nano Vol. 9; no. 5; pp. 5223 - 5233
• Main Authors: Chen, Qian, Wang, Xin, Wang, Chao, Feng, Liangzhu, Li, Yonggang, Liu, Zhuang
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 26.05.2015
• Subjects: Animals; Cell Line, Tumor; Cell Transformation, Neoplastic; Combined Modality Therapy; Female; Glioblastoma - drug therapy; Glioblastoma - pathology; Humans; Hydrophobic and Hydrophilic Interactions; Mice; Models, Molecular; Molecular Targeted Therapy; Oligopeptides - chemistry; Oligopeptides - metabolism; Paclitaxel - pharmacology; Paclitaxel - therapeutic use; Porphyrins - pharmacology; Protein Aggregates; Protein Conformation; Serum Albumin - chemistry; Serum Albumin - metabolism; Theranostic Nanomedicine - methods; paclitaxel; self-assembly; combination therapy; cancer targeting; human serum albumin
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.5b00640

Paclitaxel (PTX) can bind to human serum albumin (HSA) via hydrophobic interaction, forming Abraxane, which is a U.S. Food and Drug Administration (FDA) approved effective antitumor nanomedicine drug. Herein, the effective antitumor drug PTX is used to induce the self-assembly of HSA modified with either a photosensitizer chlorin e6 (Ce6), which at the same time serves as a chelating agent for Mn2+ to enable magnetic resonance imaging, or acyclic Arg-Gly-Asp (cRGDyK) peptide that targets αvβ3-integrin overexpressed on tumor angiogenic endothelium. Two types of tumor-targeting theranostic nanoparticles are constructed, either by coassembly of both HSA-Ce6 and HSA-RGD simultaneously or by forming an HSA-Ce6@HSA-RGD core–shell structure, with the assistance of PTX-induced albumin aggregation. Such albumin-based nanoparticles on one hand could targetαvβ3-integrin, as evidenced by both in vitro and in vivo experiments, and on the other hand enable combined photodynamic/chemotherapy, which offers remarkably improved therapeutic efficacy to kill cancer in comparison to the respective monotherapies. Our work presents a new type of tumor-targeted multifunctional albumin-based nanoparticles by drug-induced self-assembly, which is a rather simple method without any sophisticated chemistry or materials engineering and is promising for multimodel imaging-guided combination therapy of cancer.