Intracellular Self‐Assembly of Nanoprobes for Molecular Imaging

Abstract

being conjugated with targeting warheads and loaded with a large number of diverse imaging agents, the multifunctional NPs are fabricated for multimodal imaging with enhanced imaging sensitivity and selectivity. Second, the uptake of NPs with appropriate size by the kidney (renal clearance) and reticular endothelial system of the liver is lower. Therefore, increased circulation time and more chances to reach the target site are achieved by NPs than small molecules. [6] Third, due to the enhanced permeability and retention effect induced by the fenestrated vasculature structures, NPs are more efficiently accumulated at the vascular angiogenic sites like tumors. [7] Fourth, once uptaken by the cells (or tissues), NPs always have longer retention time (i.e., aggregation/assembly-induced retention effect) in the cells (or the bodies) than small molecular probes, which is good for molecular imaging. [8] Nevertheless, NPs always face the problems of reproducibility and quantification, difficulty in their fabrication, as well as cell membrane translocation when applied for molecular imaging. [9] Luckily, a "smart" intracellular self-assembly strategy emerged at the right moment to overcome the above limitations of NPs, which starts with a small molecular probe to quickly translocate cell membrane but ends up with nanostructures (nanoparticles or nanofibers) with amplified imaging signals and longer retention time at the targeted sites. Intracellular Self-Assembly of NanoprobesSelf-assembly is a prevalent and important process in nature, for example, the 25 nm wide microtubules to govern cellular mitosis, 5-6 nm thick cell membranes to maintain cell integrity, and 2 nm wide DNA double strand to store genetic information are the typical presentations of molecular self-assembly in biological systems. [10] Molecular self-assembly is a "bottomup" fabrication process in which small building blocks selfassemble through various noncovalent interactions (e.g., π-π stacking, hydrogen bonding, metal coordination, host-guest interaction, electrostatic, hydrophobic, and van der Waals interactions) to build up highly ordered nanostructures. [11] Up to date, lots of self-assembly systems have been developed to ex situ or in situ fabricate biocompatible nanomaterials for biomedical applications. [8] Compared with ex situ self-assembly, in situ self-assembly (e.g., intracellular self-assembly) in which small molecules transform into nanoprobes under intelligent Molecular imaging can be roughly defined as the characterization and measurement of biological processes at the molecular and cellular level. Nanoprobes (NPs) are advantageous over small molecular probes for molecular imaging in the amount of signaling molecule as well as signal intensity. Compared with ex situ self-assembling strategies for NP fabrication, those intracellular intelligent self-assembling strategies that use small molecules to prepare NPs in situ with amplified signals and longer retention time are more efficient and attractive. This review summarizes recent adva...

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Intracellular Bottom‐up Synthesis of Ultrasmall CuS Nanodots in Cancer Cells for Simultaneous Photothermal Therapy and COX‐2 Inactivation

“…Such a strategy has been applied to enhance MRI imaging signals and increase drug penetration and retention in solid tumors. [ 16–21 ] Nevertheless, such an iBuS strategy has never been investigated for PTT.…”

A Versatile Linker for Probes Targeting Hydrolases via In Situ labeling

“…Various strategies have been developed to improve the spatial resolution. [6][7][8] For example, small molecule probes can be activated by the target enzyme, and due to the change in hydrophobicity before and after enzyme activation, they can self-assembly into nanometersized particles or aggregates and retain at site of activation. [9][10][11][12][13][14][15][16] Another strategy is to form a covalent bond between the reporter moiety and intracellular proteins via the reaction between a labile electrophilic moiety on the imaging probe and nucleophiles such as thiols or amines on proteins.…”