In Vivo Tumor-Targeted Dual-Modality PET/Optical Imaging with a Yolk/Shell-Structured Silica Nanosystem

Silica nanoparticles have been one of the most promising nanosystems for biomedical applications due to their facile surface chemistry and non-toxic nature. However, it is still challenging to effectively deliver them into tumor sites and noninvasively visualize their in vivo biodistribution with excellent sensitivity and accuracy for effective cancer diagnosis. In this study, we design a yolk/shell-structured silica nanosystem ^(64) Cu-NOTAQD@HMSN-PEG-TRC105, which can be employed for tumor vasculature targeting and dual-modality PET/optical imaging, leading to superior targeting specificity, excellentimaging capability and more reliable diagnostic outcomes.By combining vasculature targeting, pH-sensitive drug delivery, and dual-modality imaging into a single platform,as-designed yolk/shell-structured silica nanosystems may be employed for the future image-guided tumor-targeted drug delivery, to further enable cancer theranostics.

In vitro study of enhanced photodynamic cancer cell killing effect by nanometer-thick gold nanosheets

Photodynamic therapy(PDT)by near-infrared(NIR)irradiation is a promising technique for treating various cancers.Here,we reported the development of free-standing wafer-scale Au nanosheets(NSs)that exhibited an impressive PDT effect.The Au NSs were synthesized by ionic layer epitaxy at the air-water interface with a uniform thickness in the range from 2 to 8.5 nm.These Au NSs were found very effective in generating singlet oxygen under NIR irradiation.In vitro cellular study showed that the Au NSs had very low cytotoxicity and high PDT efficiency due to their uniform 2D morphology.Au NSs could kill cancer cells after 5 min NIR irradiation with little heat generation.This performance is comparable to using 10 times mass loading of Au nanoparticles(NPs).This work suggests that two-dimensional(2D)Au NSs could be a new type of biocompatible nanomaterial for PDT of cancer with an extraordinary photon conversion and cancer cell killing efficiency.

General synthesis of silica-based yolk/shell hybrid nanomaterials and in vivo tumor vasculature targeting

Multifunctional yolk/shell-structured hybrid nanomaterials have attracted increasing interest as theranostic nanoplatforms for cancer imaging and therapy. However, because of the lack of suitable surface engineering and tumor targeting strategies, previous research has focused mainly on nanostructure design and synthesis with few successful examples showing active tumor targeting after systemic administration. In this study, we report the general synthetic strategy of chelator-free zirconium-89 （89Zr）-radiolabeled, TRC105 antibody-conjugated, silica-based yolk/sheU hybrid nanopartides for in vivo tumor vasculature targeting. Three types of inorganic nanoparticles with varying morphologies and sizes were selected as the internal cores, which were encapsulated into single hollow mesoporous silica nanosheUs to form the yolk/sheU-structured hybrid nanopartides. As a proof-of-concept, we demonstrated successful surface functionalization of the nanoparticles with polyethylene glycol, TRC105 antibody （specific for CD105/endoglin）, and ~Zr （a positron-emitting radioisotope）, and enhanced in vivo tumor vasculature-targeted positron emission tomography imaging in 4T1 murine breast tumor-bearing mice. This strategy could be applied to the synthesis of other types of yolk/shell theranostic nanoparticles for tumor- targeted imaging and drug delivery.