NIR-II Perylene Monoimide-Based Photothermal Agent with Strengthened Donor-Acceptor Conjugation for Deep Orthotopic Glioblastoma Phototheranostics.

Extensive efforts have been devoted to the design of organic photothermal agents (PTAs) that absorb in the second near-infrared (NIR-II) bio-window, which can provide deeper tissue penetration that is significant for phototheranostics of lethal brain tumors. Herein, the first example of NIR-II-absorbing small organic molecule (N1) derived from perylene monoamide (PMI) and its bio-application after nano-encapsulation of N1 to function as a nano-agent for phototheranostics of deep orthotopic glioblastoma (GBM) is reported. By adopting a dual modification strategy of introducing a donor-acceptor unit and extending π-conjugation, the obtained N1 can absorb in 1000-1400 nm region and exhibit high photothermal conversation due to the apparent intramolecular charge transfer (ICT). A choline analogue, 2-methacryloyloxyethyl phosphorylcholine, capable of interacting specifically with receptors on the surface of the blood-brain barrier (BBB), is used to fabricate the amphiphilic copolymer for the nano-encapsulation of N1. The obtained nanoparticles demonstrate efficient BBB-crossing due to the receptor-mediated transcytosis as well as the small nanoparticle size of approximately 26 nm. The prepared nanoparticles exhibit excellent photoacoustic imaging and significant growth inhibition of deep orthotopic GBM. The current study demonstrates the enormous potential of PMI-based NIR-II PTAs and provides an efficient phototheranostic paradigm for deep orthotopic GBM.

A facile design of thio-perylenediimides with controllable fluorescent, photodynamic and photothermal effects towards cancer theranostics.

A series of thionated perylenediimides with modulating phototheranostic modalities have been synthesized by a one-pot method for multiple anti-cancer applications. Compared to the initial and 4-tert-butyl phenol-substituted fluorescent perylenediimide, the obtained monothionated perylenediimide became photodynamic. With the increase of thionation degree, tetrathionated perylenediimide changed into an optimal photothermal agent.

T-box transcription factors Dorsocross and optomotor-blind control Drosophila leg patterning in a functionally redundant manner.

The T-box genes are essential transcription factors during limb development. In Drosophila, Dorsocross (Doc) and optomotor-blind (omb), members of the Tbx2 and Tbx6 families, are best studied in the Drosophila wing development. Despite prominently expressed in leg discs, the specific function of these genes in leg growth is still not revealed. Here we demonstrated that Doc and omb regulated the morphogenesis of leg intermediate regions in a functionally redundant manner. Loss of Doc or omb individually did not result in any developmental defects of the legs, but loss of both genes induced significant defects in femur and proximal tibia of the adult legs. These genes located in the dorsal domain, where the Doc region expanded and cross-overlapped with the omb region corresponding to the presumptive leg intermediate region. We detected that the normal epithelial folds in the leg discs were disrupted along with dorsal repression of cell proliferation and activation of cell apoptosis when Doc and omb were both reduced. Furthermore, the dorsal expression of dachshund (dac), a canonical leg developmental gene specifying the leg intermediate region, was maintained by Doc and omb. Meanwhile, the Notch pathway was compromised in the dorsal domain when these genes were reduced, which might contribute to the joint defect of the adult leg intermediate regions. Our study provides cytological and genetic evidence for understanding the redundant function of Doc and omb in leg morphogenesis.