3 years ago

Enhancing Therapeutic Efficacy of Combined Cancer Phototherapy by Ultrasound-Mediated In Situ Conversion of Near-Infrared Cyanine/Porphyrin Microbubbles into Nanoparticles

Enhancing Therapeutic Efficacy of Combined Cancer Phototherapy by Ultrasound-Mediated In Situ Conversion of Near-Infrared Cyanine/Porphyrin Microbubbles into Nanoparticles
Yunxue Xu, Jinrui Wang, Shumin Wang, Yiming Zhou, Ligang Cui, Xiaolong Liang, Huiyu Ge, Wen Chen, Pravin Bhattarai, Yang Sun, Zhifei Dai
Nanoparticles (NPs)-based diagnosis and phototherapy are emerging as the cutting-edge technologies for detection and treatment of cancer but their applications are still limited since insufficient and heterogeneous NPs accumulation in cancer often causes recurrence. To overcome these limitations, multifunctional microbubbles (MBs) were constructed with 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindotricarbocyanine iodide (DiR) and porphyrin grafted lipid (PGL). Both DiR and PGL self-assembled as microbubbles, the as-designed PGL-DiR MBs possess remarkably high drug loading contents (5.8% PGL and 10.38% DiR) and stable co-delivery drug combinations. In vivo experiments showed PGL-DiR MBs could serve as an excellent ultrasound contrast agent to enhance ultrasound imaging greatly for identifying the location and size of the tumors. Upon exposure to ultrasound, in situ conversion of PGL-DiR MBs into nanoparticles resulted in a remarkable increase in fluorescence intensity (~5 folds) in tumor compared with PGL-DiR NPs, validating the enhanced tumor accumulation and cellular uptake of therapeutic agents. PGL-DiR MBs showed complete tumor ablation without recurrence in vivo, while PGL-DiR NPs showed only 72.6% tumor growth inhibition at the same dose. We believe that PGL-DiR MBs will soon reach their full potential as an important class of phototherapeutic formulations and will contribute to remarkable advances in cancer treatments. The multifunctional PGL-DiR MBs, fabricated with 1, 1-dioctadecyl-3, 3, 3, 3-tetramethylindotricarbocyanine iodide (DiR) and porphyrin grafted lipid (PGL), possess remarkably high drug loading contents and could serve as an excellent ultrasound contrast agent. Upon exposure to ultrasound, in situ conversion of PGL-DiR MBs into nanoparticles, compared with PGL-DiR NPs, resulted in enhanced tumor accumulation and cellular uptake of therapeutic agents.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/adfm.201704096

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