Non‐invasive, real‐time, dynamic, and quantitative molecular imaging has been developed to facilitate disease diagnosis, drug development, and pathological analysis at the molecular level. Qualitative and quantitative analysis and imaging of physiological processes at the molecular level can be achieved with advanced molecular imaging by employing imaging contrast agents in combination with traditional imaging modalities, such as optical imaging, ultrasound imaging, magnetic resonance imaging, single‐photon emission computed tomography, and positron emission tomography. With the aid of molecular imaging, absorption, distribution, metabolism, excretion, and other processes of drugs in various animals can be monitored quantitatively, and in vivo pharmacokinetics and pharmacodynamics can be simulated before clinical trials, which significantly shorten the period for drug development and reduce the number of animals participating in various tests. Here, the role of molecular imaging in drug target validation, drug screening, drug sensitivity analysis, pharmacokinetics research, drug efficacy evaluation, and other processes of chemical and biological drug research and development is summarized. Molecular imaging has become a powerful and effective tool in the research and development of various drugs for the treatment of a variety of diseases. Advanced molecular imaging can provide important support for disease and drug research, which will accelerate drug discovery and development.

The emerging technique of photoacoustic imaging, especially in the near infra-red (NIR) window, permits high resolution, deep-penetration, clinically reliable sensing. However, few contrast agents are available that can specifically respond to intricate biological environments, and which are biodegradable and biocompatible. Herein, we introduce a new class of pH-sensitive organic photoacoustic contrast agent that operates in the second NIR window (NIR-Ⅱ, 960–1, 700 nm), which is derived from the self-assembled charge-transfer nanocomplex (CTN) by 3, 3', 5, 5'-tetramethylbenzidine (TMB) and its dication structure (TMB⁺⁺). The unique NIR-Ⅱ-responsive CTN can specifically respond to pH change in the physiological range and allows noninvasive and sensitive visualization of the tumor acidic microenvironment (e.g. at pH 5) in mice with higher signal-to-noise ratio. The CTN is biodegradable under physiological conditions (e.g. pH 7.4), which alleviates the biosafety concern of nanoparticle accumulation in vivo. These results clearly show the potential of the TMB/TMB⁺⁺-based CTN as a promising pH-activated and biodegradable molecular probe for specific tumor photoacoustic imaging in the NIR-Ⅱ region.

Precision medicine is a potential effective therapeutic for various human diseases. Currently, metal complex-based drugs are being successfully used in clinical applications owing to diverse properties such as multiple redox states, photo-induced ligand exchange, and preferential ligand and coordination numbers, which facilitate drug design and development. However, drawbacks such as toxicity, lack of specificity, and severe side effects have hampered their therapeutic outcome. Therefore, innovative strategies for improving the specificity and pharmacokinetics of conventional metal complex-based therapeutic agents are required. Recently, nanotechnology, which provides a unique toolbox for developing effective and safer medicine, has attracted considerable attention, mainly because of their ability to reduce side effects and enhance drug loading efficiency and pharmacokinetics. Considering the promising chemical and physical properties of diverse nanostructures, nanoformulation of metal complexes can be used to effectively address the problems associated with current metallodrug complexes, especially those based on stimuli-responsive therapeutic strategies, with excellent spatial, temporal, and dosage control. In this review, we have mainly focused on the specificity and environment-responsiveness of metallodrug nanoformulations as therapeutics, and summarized the recent strategies being used for developing metal complex-functionalized intelligent nanoplatforms, which respond to various types of stimuli, including endogenous signals (pH, redox conditions, and enzyme activities) or external triggers (light irradiation and magnetic field manipulations). In addition, we have also discussed the potential challenges associated with use of metallodrugs and their nanoformulations as effective precision therapy with improved specificity and minimal side effects.