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

Abstract

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 Mn(2+) 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.

• Authors: Qian Chen, Xin Wang, Chao Wang, Liangzhu Feng, Yonggang Li, Zhuang Liu
• Journal: ACS nano (ACS Nano) Vol. 9 Issue 5 Pg. 5223-33 (May 26 2015) ISSN: 1936-086X [Electronic] United States
• PMID: 25950506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Chlorophyllides
• Oligopeptides
• Porphyrins
• Protein Aggregates
• Serum Albumin
• phytochlorin
• arginyl-glycyl-aspartic acid
• Paclitaxel

Topics

• Animals
• Cell Line, Tumor
• Cell Transformation, Neoplastic
• Chlorophyllides
• Combined Modality Therapy
• Female
• Glioblastoma (drug therapy, pathology)
• Humans
• Hydrophobic and Hydrophilic Interactions
• Mice
• Models, Molecular
• Molecular Targeted Therapy
• Oligopeptides (chemistry, metabolism)
• Paclitaxel (pharmacology, therapeutic use)
• Porphyrins (pharmacology)
• Protein Aggregates
• Protein Conformation
• Serum Albumin (chemistry, metabolism)
• Theranostic Nanomedicine (methods)