Facile Synthesis of a Multifunctional Porous Organic Polymer Nanosonosensitizer (mHM@HMME) for Enhanced Cancer Sonodynamic Therapy.

Sonodynamic therapy (SDT), which involves the activation of sonosensitizers to generate cytotoxic reactive oxygen species under ultrasound irradiation, is a promising noninvasive modality for cancer treatment. However, the clinical translational application of SDT is impeded by the lack of efficient sonosensitizers, the inefficient accumulation of sonosensitizers at tumor sites, and the complicated immunosuppressive tumor microenvironment. Herein, we developed a facilely synthesized multifunctional porous organic polymer nanosonosensitizer (mHM@HMME) for enhanced SDT. Specifically, mHM@HMME nanosonosensitizers were prepared by incorporating chemotherapeutic mitoxantrone into the one-step synthesis process of disulfide bond containing porous organic polymers, followed by loading with organic sonosensitizer (HMME) and camouflaging with a cancer cell membrane. Due to the cancer cell membrane camouflage, this multifunctional mHM@HMME nanosonosensitizer showed prolonged blood circulation and tumor targeting aggregation. Under ultrasound irradiation, the mHM@HMME nanosonosensitizer exhibited a satisfactory SDT performance both in vitro and in vivo. Moreover, the potent SDT combined with glutathione-responsive drug release in tumor cells induced robust immunogenic cell death to enhance the antitumor effect of SDT in turn. Overall, this facilely synthesized multifunctional mHM@HMME nanosonosensitizer shows great potential application in enhanced SDT.

Gene-engineered exosomes-thermosensitive liposomes hybrid nanovesicles by the blockade of CD47 signal for combined photothermal therapy and cancer immunotherapy.

CD47, overexpressed on kinds of tumor cells, activates a "don't eat me" signal through binding to signal regulatory protein α (SIRPα), leading to immune escape from the mononuclear phagocyte system (MPS). It is also a huge challenge to deliver therapeutic drugs to the tumor sites due to the short retention time in blood, poor targeting of tumor cells and accelerated clearance by MPS. Herein, we designed a hybrid therapeutic nanovesicles, named as hGLV, by fusing gene-engineered exosomes with drug-loaded thermosensitive liposomes. We demonstrated that the CD47-overexpressed hGLV exhibited the long blood circulation and improved the macrophages-mediated the phagocytosis of tumor cells by blocking CD47 signal. Moreover, the resulted hGLV could remarkably target the homologous tumor in mice, achieving the preferential accumulation at the tumor sites. Importantly, hGLV loading the photothermal agent could achieve the excellent photothermal therapy (PTT) under laser irradiation after the intravenous injection, completely eliminating the tumors, leading to immunogenic cell death and generating substantial tumor-associated antigens, which could promote the maturation of immature dendritic cells with the help of the co-encapsulated immune adjuvant to trigger strong immune responses. Generally, the hybrid nanovesicles based on CD47 immune check point blockade can be a promising platform for the drug delivery in cancer treatment.

Perfluorohexane-Loaded Polymeric Nanovesicles with Oxygen Supply for Enhanced Sonodynamic Therapy.

Sonodynamic therapy (SDT), as a new method of non-invasive tumor treatment developed from photodynamic therapy (PDT), can overcome the disadvantage of poor laser penetration while retaining the function of PDT. However, the lack of efficient sonosensitizer accumulation and the hypoxic environment in tumor sites limited the therapeutic efficacy of SDT. Here, we constructed a highly efficient liquid fluorocarbon-encapsulated polymeric nanovesicle for enhanced sonodynamic efficacy as well as tumor hypoxia relief. This multifunctional nanovesicle was constructed by fluorinated cationic polymer C9F17-PAsp(DET) with PEG-conjugated protoporphyrin IX (PEG-PpIX) modification, which could yield the simultaneous loading of perfluorohexane (PFH) and oxygen. We found that the PAsp(DET)-PpIX-PEG@PFH nanovesicles could not only generate the reactive oxygen species (ROS) under ultrasound irradiation after intravenous (i.v.) injection but also could generate and prolong the ROS under nanovesicle preparation by ultrasonication in vitro, so-called the ″exogenous ROS", which might result in enhanced cytotoxicity in tumor tissue. Furthermore, oxygen-loaded PAsp(DET)-PpIX-PEG nanovesicles could not only reduce therapeutic resistance by relieving tumor hypoxia but also increase ROS production for enhanced sonodynamic therapy. An in vivo study revealed that the nanovesicles could accumulate in the tumor site after i.v. injection and achieved remarkable tumor growth inhibition in both with and without preloaded oxygen groups, which indicated that the nanovesicle system could efficiently achieve oxygen loading during in vivo circulation and provide a better solution for SDT application.

[Non-osteogenic malocclusion after anatomic reduction and miniplate rigid fixation in condylar neck and subcondylar fractures].

OBJECTIVE: To analysis the cause of malocclusion that was found in patients suffering from condylar neck and subcondylar fractures after perfectly anatomic reduction and rigid fixation. METHODS: There were 23 cases of malocclusion in the patients of condylar neck and subcondylar fractures after anatomic reduction and rigid fixation during 1994 to 2001. The possible reasons were studied, and the treatment methods were proposed. RESULTS: Both distortion and(or) fracture of miniplates and displacement anain of the condylar process after operation were not found in all 23 cases. There were 6 cases of open bite at the molar teeth of the fractured side, while the normal occlusions were showed in the nonfractured side. 11 cases showed that the whole mandibles were moved slightly to the nonfractured side. 4 cases showed that the mandible of fractured side moved slightly to the nonfractured side and the occlusion of nonfractured side were normal. 2 cases showed premature contact at the fractured molar teeth and the anterior teeth showed open bite. There were 5 cases of facial nerve damages, 2 cases wound infection, 2 cases TMJ chronic pain and 1 cases TMJ click and(or) murmur. CONCLUSIONS: Although the anatomical reduction and miniplate rigid fixation were operated on the condylar neck and subcondylar fractures, there were probably having the chance of showing malocclusion. The malocclusion was not caused by the fracture itself, but in the TMJ and/or muscular injury. Therefore, the malocclusion can be cured with intermaxillary elastic traction and functional exercise. Sometimes, the occlusal adjustment may be performed to resume the normal occlusion. In any case, operation is not needed.