Journal
ACS NANO
Volume 9, Issue 5, Pages 5223-5233Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.5b00640
Keywords
paclitaxel; human serum albumin; cancer targeting; self-assembly; combination therapy
Categories
Funding
- National Basic Research Programs of China (973 Program) [2012CB932600, 2011CB911002]
- National Natural Science Foundation of China [51222203, 51132006]
- Juangsu Natural Science Fund for Distinguished Young Scholars [BK20130005]
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
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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 photo-sensitizer 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 alpha v beta 3-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 target alpha v beta 3-integrin, as evidenced by both in vitro and in vivo experiments, and on the other hand enable combined photodynannic/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.
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