Neuroendocrine Tumor‐Targeted Upconversion Nanoparticle‐Based Micelles for Simultaneous NIR‐Controlled Combination Chemotherapy and Photodynamic Therapy, and Fluorescence Imaging

• Published in: Advanced functional materials 2017-02, Vol.27 (8), p.np-n/a
• Main Authors: Chen, Guojun, Jaskula‐Sztul, Renata, Esquibel, Corinne R., Lou, Irene, Zheng, Qifeng, Dammalapati, Ajitha, Harrison, April, Eliceiri, Kevin W., Tang, Weiping, Chen, Herbert, Gong, Shaoqin
• Format: Article
• Language: English
• Subjects: Anticancer properties; Block copolymers; Chemotherapy; Drug delivery systems; Energy transfer; Fluorescence; Imaging; Lithosphere; Luminescence; Materials science; Medical imaging; Micelles; Nanoparticles; Nanostructure; Near infrared radiation; neuroendocrine cancer; NIR‐controlled drug release; Photodynamic therapy; Polyethylene glycol; Polyethylenes; Segments; theranostic micelles; Tumors; Upconversion; upconversion nanoparticles
• ISSN: 1616-301X; 1616-3028
• DOI: 10.1002/adfm.201604671

Although neuroendocrine tumors (NETs) are slow growing, they are frequently metastatic at the time of discovery and no longer amenable to curative surgery, emphasizing the need for the development of other treatments. In this study, multifunctional upconversion nanoparticle (UCNP)‐based theranostic micelles are developed for NET‐targeted and near‐infrared (NIR)‐controlled combination chemotherapy and photodynamic therapy (PDT), and bioimaging. The theranostic micelle is formed by individual UCNP functionalized with light‐sensitive amphiphilic block copolymers poly(4,5‐dimethoxy‐2‐nitrobenzyl methacrylate)‐polyethylene glycol (PNBMA‐PEG) and Rose Bengal (RB) photosensitizers. A hydrophobic anticancer drug, AB3, is loaded into the micelles. The NIR‐activated UCNPs emit multiple luminescence bands, including UV, 540 nm, and 650 nm. The UV peaks overlap with the absorption peak of photocleavable hydrophobic PNBMA segments, triggering a rapid drug release due to the NIR‐induced hydrophobic‐to‐hydrophilic transition of the micelle core and thus enabling NIR‐controlled chemotherapy. RB molecules are activated via luminescence resonance energy transfer to generate 1O2 for NIR‐induced PDT. Meanwhile, the 650 nm emission allows for efficient fluorescence imaging. KE108, a true pansomatostatin nonapeptide, as an NET‐targeting ligand, drastically increases the tumoral uptake of the micelles. Intravenously injected AB3‐loaded UCNP‐based micelles conjugated with RB and KE108—enabling NET‐targeted combination chemotherapy and PDT—induce the best antitumor efficacy. Neuroendocrine tumor (NET)‐targeted upconversion nanoparticle (UCNP)‐based theranostic micelles are developed for simultaneous near‐infrared (NIR)‐controlled combination chemotherapy and photodynamic therapy (PDT), and fluorescence imaging. The NIR light can effectively trigger fast drug release at the tumor sites, thereby achieving superior chemotherapy efficacy and effectively generating 1O2 for PDT. These UCNP‐based theranostic micelles can also serve as excellent NET‐targeted imaging probes.