期刊
ACS BIOMATERIALS SCIENCE & ENGINEERING
卷 6, 期 1, 页码 474-484出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.9b01587
关键词
self-assembly; near-infrared dye; hydrophilic drug delivery; near-infrared imaging; theranostic nanoplatform
资金
- National Research Foundation of Korea [NRF-2019R1A4A1024116, NRF-2019R1A2C2085962, NRF-2018M3A9E2024583]
- Korea Research Institute of Bioscience & Biotechnology (KRIBB)
The strategy of co-loading therapeutic agents in a single nanocarrier is the most common method in theranostic cancer research. However, it is still challenging to encapsulate theranostic agents that have different physicochemical properties in a single nanocarrier system because of the immiscibility between the hydrophobic fluorescent molecule and the hydrophilic drug molecule. Thus, we report a novel concept of a theranostic nanoparticle (NP) consisting of an amphiphilic near-infrared (NIR) dye as a hydrophilic drug delivery carrier with enhanced NIR imaging capability. Unlike conventional nanocarrier systems, the newly designed amphiphilic NIR dyes (Cy-C dyes) function as both the drug delivery carrier and the fluorescent imaging agent. It can be utilized for therapy and diagnosis simultaneously by simply encapsulating the hydrophilic drug. This method is innovative not only due to formation of the theranostic nanoparticle for immiscible hydrophilic drug delivery but also because of generation of strong fluorescence signals due to the Cy-C dyes on the surfaces of the NPs. In this study, Cy-C (C = C3, C6, and C9) dyes were designed by conjugating the heptamethine cyanine dye with poly(ethylene glycol) (PEGSK) and polyethyleneimine 2000 (PEI2K). The result was self-assembled structures that effectively encapsulated a hydrophilic drug molecule (MTX) without self-quenching and scattered light interference. Among the Cy-C NPs encapsulating MTX (Cy-C/MTX NPs), Cy-C6/MTX and Cy-C9/MTX formed a concentric supramolecular bilayer (like liposomes in aqueous solution) and were capable of translocating hydrophilic drug molecules to their aqueous interior spaces. The supramolecular bilayer structure of Cy-C9/MTX provides better particle stability and drug delivery efficacy than does the supramolecular monolayer structure of Cy-C3/MTX. In addition, Cy-C9/MTX demonstrated excellent blood circulation and long-term tumor retention qualities in living mice. The effective tumor suppression ability of Cy-C9/MTX validated the concept that the amphiphilic Cy-C9 dye is the best nanoplatform for theranostics based on hydrophilic drug delivery.
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