适体
化学
费斯特共振能量转移
插层(化学)
生物物理学
荧光寿命成像显微镜
DNA
荧光
小分子
立体化学
组合化学
分子生物学
生物化学
生物
物理
量子力学
无机化学
作者
Wenjie Ma,Huanhuan Sun,Biao Chen,Ruichen Jia,Jin Huang,Hong Cheng,Xiaoxiao He,Mengxi Huang,Kemin Wang
标识
DOI:10.1021/acs.analchem.1c03580
摘要
Herein, we subtly engineered a pH and membrane receptor dual-activatable aptamer therapeutic for bispecific tumor cell imaging and in situ drug release by utilizing a hairpin-contained i-motif as the acid-responsive element to be complementary with a tumor-targeted aptamer, named as an aptamer "molecule-doctor" (pH-Apt-MD). Specifically, the pH-Apt-MD consisted of two DNA strands, where the Apt-sgc8c was labeled with AF488 and Cy3 at its 5'- and 3'-end, respectively. The I-strand, a hairpin-contained i-motif, was complementary to the Apt-sgc8c strand partially, labeled with a BHQ2 in the middle, thus generating Cy3 with quenched fluorescence and only AF488-emitted fluorescence. The double-helix region of pH-Apt-MD was designed rich in GC bases, providing sites for doxorubicin (Dox) intercalation. Once target cells were encountered, the pH-Apt-MD disassembled due to the specific recognition of the aptamer and conformation change of the i-motif, with activated fluorescence resonance energy transfer (FRET) signals between AF488 and Cy3, accompanied by Dox release in situ. Benefiting from the design of the hairpin-contained i-motif, the pH-Apt-MD presented a narrow pH response range (pH 6.0-6.8) with a transition midpoint (pHT) of 6.50 ± 0.04. Furthermore, living cell studies revealed that the stimuli-responsive FRET signal activation of pH-Apt-MD was successfully achieved on the HCT116 cell surface with ultralow background and enhanced imaging contrast. Then, the cytotoxicity experiments proved that accurate drug release and cell killing were realized to target cells in an acidic microenvironment. As a facile double stimuli-responsive strategy, the pH-Apt-MD may hold great promise for application in precise diagnosis and therapy of cancer cells.
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