| Summary: | 碩士 === 國立交通大學 === 應用化學系分子科學碩博士班 === 108 === Recently, the drug nanocarriers have attracted extensive attention from scientists due to its unique features. In our study, we aimed to design and synthesize this type of functional particles with dual therapeutic effects. The drug-loading process involved electrostatic interaction and the drug-releasing process could be controlled by pH effect and ultrasonic treatment. To synthesize the functional particles, we firstly prepared a dendrimeric nanocluster (DNC) by using PAMAM G3 as the frame structure and further sequentially introducing indocyanine green (ICG, a sonosensitizer), pH-responsive polyacrylic acid and osimertinib (an EGFR TKI drug) onto the resulting structure to form a functional particle, I:O-NPs. We further conjugated PEG5000 and EGFR binding peptide on I:O-NPs to form the I:O-P/EP NPs for improving the biocompatibility and specificity of bio-recognition, respectively. The encapsulation efficiency (EE) of ICG and osimertinib was 94±1 % and 51±4 % with the corresponding drug loading content (DLC) of 61±1 % and 21±1 %. When the acidity was controlled at pH 5.0, the interaction between the drug molecule and the carrier was decreased, resulting in the enhancement of drug release. After ultrasonic treatment, presumably, the degradation of carrier structure occurred and, consequently, induced highly efficient drug release. Cell experiments demonstrated that I:O-P/EP NPs possess a strong affinity toward cell line A431, an EGFR highly overexpressed strain, and the stronger inhibitory effect on cell growth was thus observed a compared to that of I:O-NPs. Under ultrasound treatment, I:O-P/EP NPs generated significant amount of reactive oxygen species (ROS), which increases toxicity to cells. In summarize, we successfully designed and synthesized particles with high drug-loading capacity, active and passive target characteristics, and dual therapeutic effects on EGFR/TKI inhibition and sonodynamic therapy.
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