Ample attention has focused on cancer drug delivery via prodrug nanoparticles due to their high drug loading property and comparatively lower side effects. In this study, we designed a PEG-DOX-Cur prodrug nanoparticle for simultaneous delivery of doxorubicin (DOX) and curcumin (Cur) as a combination therapy to treat cancer. DOX was conjugated to PEG by Schiff’s base reaction. The obtained prodrug conjugate could self-assemble in water at pH 7.4 into nanoparticles (PEG-DOX NPs) and encapsulate Cur into the core through hydrophobic interaction (PEG-DOX-Cur NPs). When the PEG-DOX-Cur NPs are internalized by tumor cells, the Schiff’s base linker between PEG and DOX would break in the acidic environment that is often observed in tumors, causing disassembling of the PEG-DOX-Cur NPs and releasing both DOX and Cur into the nuclei and cytoplasma of the tumor cells, respectively. Compared with free DOX, free Cur, free DOX-Cur combination, or PEG-DOX NPs, PEG-DOX-Cur NPs exhibited higher anti-tumor activity in vitro. In addition, the PEG-DOX-Cur NPs also showed prolonged blood circulation time, elevated local drug accumulation and increased tumor penetration. Enhanced anti-tumor activity was also observed from the PEG-DOX-Cur-treated animals, demonstrating better tumor inhibitory property of the NPs. Thus, the PEG-DOX-Cur prodrug nanoparticle system provides a simple yet efficient approach of drug delivery for chemotherapy.

Near infrared (NIR) fluorescence imaging (700–900 nm) is a promising technology in preclinical and clinical tumor diagnosis and therapy. The availability of excellent NIR fluorescent contrast agents is still the main barrier to implementing this technology. Herein, we report the design and synthesis of two series of NIR fluorescent molecules with long wavelength excitation and aggregation-induced emission (AIE) characteristics by fine-tuning their molecular structures and substituents. Further self-assembly between an amphiphilic block co-polymer and the obtained AIE molecules leads to AIE nanoparticles (AIE NPs), which have absorption maxima at 635 nm and emission maxima between 800 and 815 nm with quantum yields of up to 4.8% in aggregated states. In vitro and in vivo toxicity results demonstrate that the synthesized AIE NPs are biocompatible. Finally, the synthesized AIE NPs have been successfully used for image-guided tumor resection with a high tumor-to-normal tissue signal ratio of 7.2.

An aggregation-induced emission luminogen (AIEgen)-based probe with both fluorescence and photoactivity activatable characteristics is developed for cancer theranostics.

Supramolecular nanofibers of proteins and peptides could be used for intracellular protein delivery.

Biocompatible peptide-based supramolecular hydrogel has recently emerged as a new and promising system for biomedical applications. In this work, Rhodamine B is employed as a new capping group of self-assembling peptide, which not only provides the driving force for supramolecular nanofibrous hydrogel formation, but also endows the hydrogel with intrinsic fluroescence signal, allowing for various bioimaging applications. The fluorescent peptide nanofibrous hydrogel can be formed via disulfide bond reduction. After dilution of the hydrogel with aqueous solution, the fluorescent nanofiber suspension can be obtained. The resultant nanofibers are able to be internalized by the cancer cells and effectively track the HeLa cells for as long as 7 passages. Using a tumor-bearing mouse model, it is also demonstrated that the fluorescent supramolecular nanofibers can serve as an efficient probe for tumor imaging in a high-contrast manner.