Smart Self-Assembled Organic Nanoprobe for Protein-Specific Detection: Design, Synthesis, Application, and Mechanism Studies

Abstract

Specific detection or imaging protein has high potential to contribute greatly to medical diagnosis, biological research, and therapeutic applications. The level of human serum albumin (HSA) in blood is related to a variety of diseases and thus serves as an important biomarker for fast clinical diagnosis. Here we report the use of aggregation-induced emission (AIE) based supramolecular assembly to design biomolecular responsive smart organic nanomaterials for detection protein HSA. The designed nanoprobes were aggregates of small molecules and silent in fluorescence, but in the presence of HSA they disassembled and produced a clear turn-on fluorescent signal. Of a small library of nanoprobes constructed for HSA detection, structure-optical signaling and screening studies revealed that nanoprobe 7 is the most efficient one. Mechanism studies showed that nanoprobe 7 was bonded with Site I of HSA through the multiple noncovalent interactions. The resultant restriction of intramolecular rotation of nanoprobe 7 in the hydrophobic cavity of HSA induced fluorescent emission, which was validated by competitive binding assays and molecular docking. More importantly, nanoprobe 7 was successfully applied to recognize and quantify HSA in human serum samples. This study demonstrates nanoprobe 7 is a promising tool for clinical real and fast detection of HSA and thus may find many applications, and the molecular assembly based on AIE also opens a new avenue for designing smart nanomaterials for the sensitive and selective detection for varied analytes.

Mixed and Matched Metallo‐Nanotexaphyrin for Customizable Biomedical Imaging

“…The approach is not without hurdles, as discovering and synthesizing inherently multifunctional building blocks, particularly those made of organic molecules, is of significant difficulty. This is reflected in the limited number of reported organic‐based multifunctional building blocks, such as bola‐type small molecules containing substituted imidazoles and pyridiniums, indocyanine green, and camptothecin drug amphiphiles …”

Novel Self-assembled Organic Nanoprobe for Molecular Imaging and Treatment of Gram-positive Bacterial Infection

“…Molecular self-assembly is a spontaneous association of individual components into well-ordered structures assisted by non-covalent interactions including electrostatic interaction, hydrogen bonding, π-π interaction, charge-transfer interactions, and hydrophobic effect 60 , 61 . Among the reported self-assembled nano-materials, small molecule self-assembled nanomaterials have received much attention for their photo-stability, biocompatibility, diversity, and flexibility in molecular design 62 - 64 . However, to the best of our knowledge, the usage of small molecule self-assembled nanomaterials in diagnostic and therapeutic platforms against microbial infections is still lacking.…”

Twisted-Intramolecular-Charge-Transfer-Based Turn-On Fluorogenic Nanoprobe for Real-Time Detection of Serum Albumin in Physiological Conditions

“…57 Compared with several self-assembling metallic and polymer nanoparticles, 58,59 only a handful of small-moleculebased nanoparticles have been exploited until now in proteinsensing applications based on disaggregation or disassembly approaches. 57,60,61 In contrast, there is a report that suggests that some near-infrared (NIR) dyes may even interact with human serum albumin (HSA) to form HSA−dye nanoparticles. 62 Hence, developing a simple and easy-to-operate small-molecule (nonpolymer) fluorogenic nanoprobe for the selective detection of serum-albumin protein (HSA) in biofluids remains a challenging task.…”