Multifunctional Supramolecular Materials Constructed from Polypyrrole@UiO-66 Nanohybrids and Pillararene Nanovalves for Targeted Chemophotothermal Therapy.

Multifunctional supramolecular nanomaterials capable of targeted and multimodal therapy hold great potential to improve the efficiency of cancer therapeutics. Herein, we report a proof-of-concept nanoplatform for effective chemophotothermal therapy via the integration of folic acid-based active targeting and supramolecular nanovalves-based passive targeting. Inspired by facile surface engineering and designable layer-by-layer assembly concept, we design and synthesize PPy@UiO-66@WP6@PEI-Fa nanoparticles (PUWPFa NPs) to achieve efficient synergistic chemophotothermal therapy, taking advantage of the desirable photothermal conversion capability of polypyrrole nanoparticles (PPy NPs) and high drug-loading capacity of hybrid scaffolds. Significantly, pillararene-based pseudorotaxanes as pH/temperature dual-responsive nanovalves allow targeted drug delivery in pathological environment with sustained release over 4 days, which is complementary to photothermal therapy, and folic acid-conjugated polyethyleneimine (PEI-Fa) at the outmost layer through electrostatic interactions is able to enhance tumor-targeting and therapeutic efficiency. Such PUWPFa NPs showed efficient synergistic chemophotothermal therapy of cervical cancer both in vitro and in vivo. The present strategy offers not only the distinctly targeted drug delivery and release, but also excellent tumor inhibition efficacy of simultaneous chemophotothermal therapy, opening a new avenue for effective cancer treatment.

[Expression of MMP-2 in the periodontal tissues with the mini-screw for molar intrusion with cyclic intrusive force in dogs].

PURPOSE: To observe the expression of MMP-2 in the periodontal tissues of molars in Beagle dogs after different times of intrusion by mini-screw with cyclic intrusive force. METHODS: Three mature Beagle dogs were used for the experiment. On the buccal and palatal sites of the left maxillary second and third premolars, a minis-crew was placed at the inter-radicular septa separately, intruding the tooth with 150 g initial force, which would be reinforced every 4 weeks. The teeth of left side as the experimental group were divided into 3 subgroups, as being intruded 12, 24 and 36 weeks, and the right side as blank control. Then the dogs were sacrificed, and the second and the third premolars with the surrounding periodontal tissue were cut down, fixed, decalcified, wrapped and cut into slices. Immunohistochemical staining with MMP-2 was performed. The average optical density (OD) of MMP-2 was calculated with IPP software, which represented the expression of MMP-2. SPSS 17.0 software package was used for statistical analysis. RESULTS: Immunohistochemical staining revealed that the expression of MMP-2 in control group was low. After tooth intrusion, MMP-2 expression significantly increased in the periodontal tissues of molars, and reached the maximum in the group of 24 weeks. Then MMP-2 expression decreased in the 36-week group but still significantly higher than the control group. There was no significant difference among the 3 subgroups for different intrusion times(P>0.05). CONCLUSIONS: MMP-2 participates in remodeling of the periodontal tissue during tooth intrusion. The expression of MMP-2 is not significantly increased with the extension of the intrusion time with cyclic intrusive force, which suggests that with the use of mini-screw to intrude the molars with cyclic intrusive force, the periodontal tissues of the intruded tooth maintain dynamic balance of bone remodeling.