Delivery of size-controlled long-circulating polymersomes in solid tumours, visualized by quantum dots and optical imaging in vivo
2015
Bakalova, Rumiana | Lazarova, Desislava | Nikolova, Biliana | Atanasova, Severina | Zlateva, Genoveva | Zhelev, Zhivko | Aoki, Ichio
The present study was designed to investigate whether poly-ion complex hollow vesicles (polymersomes), based on chemically modified chitosan, are appropriate for passive tumour targeting in the context of their application as drug carriers. The experiments were performed on colon cancer-grafted mice. The mice were subjected to anaesthesia and injected intravenously with water-soluble nanoparticles: (1) QD⁷⁰⁵-labelled polymersomes (average size ∼120 nm; size distribution ∼10%) or (2) native QD⁷⁰⁵. The optical imaging was carried out on Maestro EX 2.10 In Vivo Imaging System (excitation filter 435–480 nm; emission filter 700 nm, longpass). In the case of QD⁷⁰⁵, the fluorescence appeared in the tumour area within 1 min after injection and disappeared completely within 60 min. A strong fluorescent signal was detected in the liver on the 30th minute. The visualization of tumour using QD⁷⁰⁵ was based only on angiogenesis. In the case of QD⁷⁰⁵-labelled polymersomes, the fluorescence appeared in the tumour area immediately after injection with excellent visualization of blood vessels in the whole body. A strong fluorescent signal was detected in the tumour area within 16 hours. This indicated that QD⁷⁰⁵-labelled polymersomes were delivered predominantly into the tumour due to their long circulation in the bloodstream and enhanced permeability and retention effect. A very weak fluorescent signal was found in the liver area. The data suggest that size-controlled long-circulating polymersomes are very promising carriers for drug delivery in solid tumours, including delivery of small nanoparticles and contrast substances.
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