Zoledronate (Zol) is a third-generation bisphosphonate that is widely used as an anti-resorptive agent for the treatment of cancer bone metastasis. While there is preclinical data indicating that bisphosphonates such as Zol have direct cytotoxic effects on cancer cells, such effect has not been firmly established in the clinical setting. This is likely due to the rapid absorption of bisphosphonates by the skeleton after intravenous (i.v.) administration. Herein, we report the reformulation of Zol using nanotechnology and evaluation of a novel nanoscale metal-organic frameworks (nMOFs) formulation of Zol as an anticancer agent. The nMOF formulation is comprised of a calcium zoledronate (CaZol) core and a polyethylene glycol (PEG) surface. To preferentially deliver CaZol nMOFs to tumors as well as facilitate cellular uptake of Zol, we incorporated folate (Fol)-targeted ligands on the nMOFs. The folate receptor (FR) is known to be overexpressed in several tumor types, including head-and-neck, prostate, and non-small cell lung cancers. We demonstrated that these targeted CaZol nMOFs possess excellent chemical and colloidal stability in physiological conditions. The release of encapsulated Zol from the nMOFs occurs in the mid-endosomes during nMOF endocytosis. In vitro toxicity studies demonstrated that Fol-targeted CaZol nMOFs are more efficient than small molecule Zol in inhibiting cell proliferation and inducing apoptosis in FR-overexpressing H460 non-small cell lung and PC3 prostate cancer cells. Our findings were further validated in vivo using mouse xenograft models of H460 and PC3. We demonstrated that Fol-targeted CaZol nMOFs are effective anticancer agents and increase the direct antitumor activity of Zol by 80 to 85% in vivo through inhibition of tumor neovasculature, and inhibiting cell proliferation and inducing apoptosis.

Activation of the innate immune system and natural killer (NK) cells has been a key effort in cancer immunotherapy research. Here, we report a nanoparticle-based trispecific NK cell engager (nano-TriNKE) platform that can target epidermal growth factor receptor (EGFR)–overexpressing tumors and promote the recruitment and activation of NK cells to eradicate these cancer cells. Moreover, the nanoengagers can deliver cytotoxic chemotherapeutics to further improve their therapeutic efficacy. We have demonstrated that effective NK cell activation can be achieved by the spatiotemporal coactivation of CD16 and 4-1BB stimulatory molecules on NK cells with nanoengagers, and the nanoengagers are more effective than free antibodies. We also show that biological targeting, either through radiotherapy or EGFR, is critical to the therapeutic effects of nanoengagers. Last, EGFR-targeted nanoengagers can augment both NK-activating agents and chemotherapy (epirubicin) as highly effective anticancer agents, providing robust chemoimmunotherapy.

Virtual Reality (VR) is being rapidly developed and bringing advancement in various related technologies through the virtual world. It has high potential and plays an important role in education and training fields. Mixed reality (MR) is a type of hybrid system that involves both physical and virtual elements. Whilst VR/ MR has proven to be an effective way to improve the learning attitude and effectiveness for secondary students, however not much work has been conducted on university students to compare the MR experience and traditional teaching approaches in learning design subjects. In this project, we investigated the effectiveness of students in learning design subjects with the support of MR. The effectiveness was measured based on their creativity and systematic approaches in design. Pre-tests and post-tests were conducted to measure the learning effects. We also compared the learning effectiveness of a student's study with the MR and traditional teaching materials. Nonparametric analyses were conducted to investigate whether the improvements were significant. Experimental results showed that after studying with the support of the MR technology, the students' abilities in geometric analysis (mean difference=4.36, p<0.01) and creativity (mean difference=1.59, p<0.05) were significantly improved. The students' ability in model visualization was also significantly better than the control group (mean difference=3.08, p<0.05). It indicated that the results were positive by using the MR to support their study. The MR was also better than using traditional teaching notes in various measured effects.