Multimodal Biophotonics of Semiconducting Polymer Nanoparticles

Biophotonics as an interdisciplinary frontier plays an increasingly important role in modern biomedical science. Optical agents are generally involved in biophotonics to interpret biomolecular events into readable optical signals for imaging and diagnosis or to convert photons into other forms of energy (such as heat, mechanical force, or chemical radicals) for therapeutic intervention and biological stimulation. Development of new optical agents including metallic nanoparticles, quantum dots, up-conversion nanoparticles, carbon dots, and silica nanoparticles has contributed to the advancement of this field. However, most of these agents have their own merits and demerits, making them less effective as multimodal biophotonic platforms. In this Account, we summarize our recent work on the development of near-infrared (NIR) semiconducting polymer nanoparticles (SPNs) as multimodal light converters for advanced biophotonics. SPNs are composed of π-electron delocalized semiconducting polymers (SPs) and often possess the advantages of good biocompatibility, high photostability, and large absorption coefficients. Because the photophysical properties of SPNs are mainly determined by the molecular structures of the precursor polymers, molecular engineering allows us to fine tune their photophysical processes to obtain different optical responses, even to light in the second NIR window (1000-1700 nm). Meanwhile, the facile nanoformulation methods of SPNs enable alteration of their outer and inner structures for diverse biological interactions. The unique photophysical properties of SPNs have brought about ultrasensitive deep-tissue molecular imaging. NIR-absorbing SPNs with strong charge-transfer backbones can convert photoenergy into mechanical acoustic waves, permitting photoacoustic imaging that bypasses the issue of light scattering and reaches the centimeter tissue penetration depth. Differently, phenylenevinylene-containing SPNs can store photon energy via chemical defects and emit long-NIR afterglow luminescence with a half-life of ∼6 min after cessation of light excitation. Such an afterglow process avoids tissue autofluorescence, giving rise to ultrahigh signal-to-background ratios. So far, SPN-based molecular photoacoustic or afterglow probes have been developed to image disease tissues (tumors), biomarkers (biothiols and reactive oxygen species), and physiological indexes (pH and temperature) in different preclinical animal models. The synthetic flexibility of SPNs further permits light-modulated biological and therapeutic interventions. Till now, SPNs with high photothermal conversion efficiencies have been shaped into photothermal transducers to remotely regulate biological events including protein ion channels, enzymatic activity, and gene expression. In conjunction with the desired biodistribution and tumor-homing ability, SPNs have been doped or coated with other inorganic agents for amplified photothermal or self-regulated photodynamic cancer therapy. This Account thus demonstrates that SPNs serve as a multimodal biophotonic nanoplatform to provide unprecedented opportunities for molecular imaging, noninvasive bioactivation, and advanced therapy.