Hongji Liu

Monovalent bispecific IgGs cater to a distinct set of mechanisms of action but are difficult to engineer and manufacture because of complexities associated with correct heavy and light chain pairing. We have created a novel design, "DuetMab," for efficient production of these molecules. The platform uses knobs-into-holes (KIH) technology for heterodimerization of 2 distinct heavy chains and increases the efficiency of cognate heavy and light chain pairing by replacing the native disulfide bond in one of the CH1-CL interfaces with an engineered disulfide bond. Using two pairs of antibodies, cetuximab (anti-EGFR) and trastuzumab (anti-HER2), and anti-CD40 and anti-CD70 antibodies, we demonstrate that DuetMab antibodies can be produced in a highly purified and active form, and show for the first time that monovalent bispecific IgGs can concurrently bind both antigens on the same cell. This last property compensates for the loss of avidity brought about by monovalency and improves selectivity toward the target cell.

Rational design of metal-free multifunctional therapeutic reagents offers great opportunities for cancer treatment in the clinic. Here, graphitic carbon nitride (g-C3N4) quantum dots embedded in carbon nanosheets (CNQD-CN) are in situ prepared via a one-pot hydrothermal approach with formamide as carbon and nitrogen source. The CNQD-CN not only serves as an excellent near-infrared (NIR) fluorescent marker but also acts as a pH-responsive nanocarrier. Moreover, the CNQD-CN possesses both light-to-heat conversion and singlet oxygen generation capabilities under a single NIR excitation wavelength. Further investigations show that systemic delivery of doxorubicin (DOX) using the multifunctional CNQD-CN nanocarrier under NIR irradiation was highly effective to cause cancer cell apoptosis in vitro and inhibit tumor growth in vivo. CNQD-CN represents a multifunctional therapeutic platform for synchronous cancer imaging and treatment through the synergistic effect of phototherapy and chemotherapy.

Graphitic carbon nitride quantum dots (g-CNQDs) have attracted much attention for biomedical applications by virtue of their good biocompatibility, stable fluorescence, high quantum yield, and nontoxicity. On the basis of understanding the intrinsic properties and structural features in the intriguing system, enormous efforts have been devoted to optimizing synthetic methods and structures of g-CNQDs. A vast number of studies have also been pursued to discuss the potential applications of g-CNQDs in biomedical areas for biosensing, bioimaging, drug delivery and theranostics. In this review, we summarize the recent advances and applications and address the future challenges and opportunities of these g-CNQDs in the biomedical field.

Visualizing deep-brain vasculature and hemodynamics is key to understanding brain physiology and pathology. Among the various adopted imaging modalities, multiphoton microscopy (MPM) is well-known for its deep-brain structural and hemodynamic imaging capability. However, the largest imaging depth in MPM is limited by signal depletion in the deep brain. Here we demonstrate that quantum dots are an enabling material for significantly deeper structural and hemodynamic MPM in mouse brain in vivo. We characterized both three-photon excitation and emission parameters for quantum dots: the measured three-photon cross sections of quantum dots are 4–5 orders of magnitude larger than those of conventional fluorescent dyes excited at the 1700 nm window, while the three-photon emission spectrum measured in the circulating blood in vivo shows a slight red shift and broadening compared with ex vivo measurement. On the basis of these measured results, we further demonstrate both structural and hemodynamic three-photon microscopy in the mouse brain in vivo labeled by quantum dots, at record depths among all MPM modalities at all demonstrated excitation wavelengths.