Dynamically assembled nanomedicine based on host-guest molecular recognition for NIR laser-excited chemotherapy and phototheranostics.

Nanomedicines combining multimodal therapeutic modalities supply opportunities to eliminate tumors in a safe and efficient manner. However, the rigid encapsulation and covalent conjugation of different therapeutic reagents suffer from the complicated preparation process, premature drug leakage and severe adverse events. Herein, we report a self-enhanced supramolecular nanomedicine (SND) based on the host-guest molecular recognition between ß-cyclodextrin (ß-CD) and camptothecin (CPT) for trimodal synergistic chemotherapy, photodynamic therapy (PDT) and photothermal therapy (PTT) using a single 670 nm near-infrared (NIR) laser. Thioketal bond and polyethylene glycol (PEG) segment are introduced into the structure of CPT-tk-PEG prodrug, thus the premature release of CPT is efficiently inhibited and the specific drug release is realized at tumor site where singlet oxygen (1O2)-generated PDT is performed. A boron dipyrromethene (BODIPY) theranostic agent is anchored onto ß-CD, endowing SND with capabilities of fluorescence imaging, PDT and PTT. Benefiting from the supramolecular assembly, not only the solubility of CPT is improved by 40 times, but also the blood circulation time and tumor accumulation of SND are greatly promoted. In vivo, SND can effectively induce the immunogenic cell death (ICD) of tumor cells, thus performing prominent inhibition against both primary and distal tumors, and even anti-metastasis effect against liver without causing obvious systemic toxicity. STATEMENT OF SIGNIFICANCE: Although nanomedicines supply opportunities to eliminate tumors in an efficient manner, they usually suffer from premature drug leakage, complicated preparation process and severe side effects owing to the rigid encapsulation or covalent conjugation. Based on the host-guest molecular recognition, we developed a self-enhanced SND for synergistic chemotherapy, photodynamic therapy and photothermal therapy. Introduction of thioketal bond in CPT prodrug avoided the premature drug release, and the specific drug release was realized in the tumor cells. Profiting from the facile supramolecular assembly strategy, SND not only displayed a primary anticancer efficacy with a low systemic toxicity, but also efficiently inhibited the growth of distal tumors, contributing a vaccine-like function to eradicate the recurrent and metastatic tumors.

Polymerization in living organisms.

Vital biomacromolecules, such as RNA, DNA, polysaccharides and proteins, are synthesized inside cells via the polymerization of small biomolecules to support and multiply life. The study of polymerization reactions in living organisms is an emerging field in which the high diversity and efficiency of chemistry as well as the flexibility and ingeniousness of physiological environment are incisively and vividly embodied. Efforts have been made to design and develop in situ intra/extracellular polymerization reactions. Many important research areas, including cell surface engineering, biocompatible polymerization, cell behavior regulation, living cell imaging, targeted bacteriostasis and precise tumor therapy, have witnessed the elegant demeanour of polymerization reactions in living organisms. In this review, recent advances in polymerization in living organisms are summarized and presented according to different polymerization methods. The inspiration from biomacromolecule synthesis in nature highlights the feasibility and uniqueness of triggering living polymerization for cell-based biological applications. A series of examples of polymerization reactions in living organisms are discussed, along with their designs, mechanisms of action, and corresponding applications. The current challenges and prospects in this lifeful field are also proposed.

Supramolecular Theranostic Nanomedicine for In Situ Self-Boosting Cancer Photochemotherapy.

Although traditional nanomedicines have enhanced the therapeutic efficacy and improved the survival quality of cancer patients, random drug release and drug resistance are deep-rooted problems hindering their clinical application. A precise nanoplatform combing chemotherapy and photodynamic therapy (PDT) is developing as a new therapeutic strategy to overcome the above challenges. Herein, a novel supramolecular nanomedicine is ingeniously constructed for in situ self-boosting cancer photochemotherapy. Hydrophilic polyethylene glycol (PEG) chains or ß-cyclodextrin (ß-CD) hosts are first conjugated onto tetraphenyl porphyrin (TCPP) to improve the solubility of TCPP and decrease their π-π stacking interactions, guaranteeing a high-efficiency PDT. Then, two camptothecin (CPT) molecules are linked together via a reactive oxygen species (ROS)-responsive thioketal bond, which averts the premature burst release of CPT and realizes in situ drug release at the tumor site where PDT is performed, resulting in an enhanced chemotherapy. Benefiting from the collaboration of host-guest complexation between ß-CD and CPT, multiple intermolecular hydrogen bonds of ß-CD, π-π stacking interactions among CPT and TCPP as well as PEG shell protection, a prolonged blood circulation time, and a selective tumor accumulation are acquired, which facilitate the synergistic photochemotherapy and bring a pre-eminent antitumor response with a low systemic toxicity.

Cucurbit[10]uril-based supramolecular radicals: Powerful arms to kill facultative anaerobic bacteria.

Two water-soluble supramolecular complexes (CB[10]⊃PSA and CB[10]⊃TPE-cyc) are constructed based on the host-guest interaction between cucurbit[10]uril (CB[10]) and perylene diimide derivative (PSA) or tetracationic cyclophane (TPE-cyc). Attributing to the matched redox potential, both supramolecular complexes can be specifically reduced into corresponding supramolecular radical cations or anions by facultative anaerobic E. coli. Benefiting from the strong near-infrared (NIR) absorption, CB[10]⊃PSA radical anions and CB[10]⊃TPE-cyc radical cations act as efficient NIR photosensitizers and perform an excellent antimicrobial activity (close to 100%) via PTT. In addition, the biocompatibility of TPE-cyc is notably improved under the protection of CB[10], guaranteeing its biosafety for in vivo application. CB[10]⊃PSA radical anions and CB[10]⊃TPE-cyc radical cations are in situ generated in the E. coli-infected abscess of mice and effectively inhibit the bacterial infection without obvious system toxicity. It is anticipated that this supramolecular strategy may pave a new way for the selective bacteria inhibition to regulate the balance of different bacterial flora.

Metal-free bioorthogonal click chemistry in cancer theranostics.

Bioorthogonal chemistry is a powerful tool to site-specifically activate drugs in living systems. Bioorthogonal reactions between a pair of biologically reactive groups can rapidly and specifically take place in a mild physiological milieu without perturbing inherent biochemical processes. Attributed to their high selectivity and efficiency, bioorthogonal reactions can significantly decrease background signals in bioimaging. Compared with metal-catalyzed bioorthogonal click reactions, metal-free click reactions are more biocompatible without the metal catalyst-induced cytotoxicity. Although a great number of bioorthogonal chemistry-based strategies have been reported for cancer theranostics, a comprehensive review is scarce to highlight the advantages of these strategies. In this review, recent progress in cancer theranostics guided by metal-free bioorthogonal click chemistry will be depicted in detail. The elaborate design as well as the advantages of bioorthogonal chemistry in tumor theranostics are summarized and future prospects in this emerging field are emphasized.

Hydrophilic Tetraphenylethene-Based Tetracationic Cyclophanes: NADPH Recognition and Cell Imaging With Fluorescent Switch.

A hydrophilic TPE-based tetracationic cyclophane TPE-cyc was synthesized, which could capture intracellular Nicotinamide adenine dinucleotide phosphate and fuel the antioxidative ability of tumor cells to detoxify reactive oxygen species (ROS). Meanwhile, upon the reduction by cellular GSH, TPE-cyc could light up tumor cells, acting as a GSH-responsive fluorescent switch to image cells with high resolution.

An investigation of bacillary dysentery outbreaks in three schools in Ankang / 中国学校卫生

Objective@#To investigate risk factors and epidemiological characteristics of bacillary dysentery outbreaks in three schools, and to provide scientific basis for the prevention and control of the epidemic in the future.@*Methods@#Case definition was established. All suspected, possible and confirmed cases of all students and faculty members from 3 schools (A, B, C) were selected for epidemiological investigation. Control group was used for case-control analysis, and relevant samples were collected for laboratory testing.@*Results@#A total of 132 cases were found in 3 schools, all of which were from students, with the incidence rate of 17.74%. The morbidity in kindergarten A was 20.00%, in center primary school B it was 21.74%, and in junior middle school C it was 11.61%. Cohort studies and casecontrol studies suggested that schools are exposed places and that washing hands with raw water in schools was possible risk factor [OR(95%CI) =4.50(1.01-20.11)]. Nine stool samples were tested in laboratory, among which 8 were positive for Shigella(88.99%), and Shigella was detected in the end nodes of school s pipeline network, the water samples from canteen bucket, and the floor drains of sewer pipe.@*Conclusion@#The bacillary dysentery outbreaks in 3 schools was caused by Shigella, which may be due to fecal contamination of domestic water in 3 schools before the start of the school year. It is suggested to strengthen the management of centralized water supply and construction in rural areas, intensify the supervision at all levels, and sanitation and disinfection before school opens at all levels.

[Treatment of lower cervical fracture dislocation by titanium screw-plate internal fixation on cervical lateral mass].

OBJECTIVE: To evaluate surgical results of the titanium screw-plate internal fixation in treatment of the lower cervical fracture dislocation. METHODS: From September 2001 to March 2006, 31 patients (24 males, 7 females; age range, 20-63 years) with the lower cervical fracture dislocation were treated in our department. The injuries were caused by a road accident in 25 patients, a high crash in 4, and a heavy object crash in 2. The fracture dislocation occurred in the following cervical segments: C3 (1 patient), C1 (5 patients), C5 (12 patients), C6 (10 patients), and C7 (3 patients). The disease course ranged from 1 to 23 days. The associated spinal nerve root injury occurred in 29 patients. The Frankle scaling revealed that 14 patients were at Grade A, 3 at Grade B, 7 at Grade C, 3 at Grade D, and 2 at Grade E (associated nerve root injury with hand and shoulder numbness). The 29 patients underwent the spinal cord decompression, the grafting fusion of the small joints, and the lateral mass titanium screw-plate internal fixation; 2 patients without nerve injury underwent only the grafting fusion of the small joints and the lateral mass titanium screw-plate internal fixation. The bone fusion, cervical vertebra movement, and internal fixation condition were observed by the X-ray examinations postoperatively. The nerve function recovery was evaluated by the Frankle scaling system. RESULTS: The followed-up in all the patients for 6 months to 4 years revealed that the small joint fusion time was 3-6 months, with an average of 3. 6 months. The cervical X-ray films showed that there was no instability or fracture looseness of the internal fixation at 6 months. Among the 29 patients with the spinal nerve root injury, 14 were at Grade A preoperatively but 13 were improved at Grade B and 1 at Grade C postoperatively; 3 were at Grade B preoperatively but 2 were improved at Grade C and 1 at Grade D postoperatively; 7 were at Grade C preoperatively but 3 were improved at Grade D and 4 at Grade E postoperatively; 3 at Grade D preoperatively but all the 3 were improved at Grade E postoperatively; 2 were at Grade E preoperatively and remained unchanged postoperatively. In the 2 patients with only the nerve root injury, numbness disappeared soon after operation. CONCLUSION: This posterior approach has two advantages: the mobility range of the cervical vertebra can preserved to the greatest extent because of the short segment fixation; the better stability can obtained because of the titanium screw-plate internal fixation on the cervical joint-column to prevent the hyperextension and hyperflexion. Therefore, the titanium screw-plate internal fixation on the cervical lateral mass is an effective treatment of the lower cervical fracture dislocation.

[Comparison of internal fixation treatment of tibia intercondylar eminence fracture between absorbable screw and metallic screw].

OBJECTIVE: To compare advantage and disadvantage of internal fixation method for tibia intercondylar eminence fracture between absorbable screw and metallic screw. METHODS: From 1996 to 2002, 200 patients with fracture of tibia intercondylar eminence were divided into group A (with absorbable screw, n = 120) and group B (with metallic screw, n = 80). And the biological compatibility, biomechanics, bone union and complications were compared between two groups. RESULTS: There were no obvious differences in operating time and circumstance of recovery position between two groups. Group A was obviously better than group B in biological compatibility, biomechanics, bone union, joint function recovery. The average healing time of group A was three months, that of group B was three and half months. The good rates of joint function in two groups were 98.0% and 95.0% respectively. The occurrence rates of wound arthritis were 1.7% and 3.7%. There was significant difference between them (P < 0.01). CONCLUSION: Absorbable screw is a more ideal material of internal fixation to treat tibia intercondylar eminence fracture.

[Clinical study on two internal fixation methods Kaneda and Z-plate in the operation of anterior surgical approach after thoracolumbar fractures].

OBJECTIVE: To study the difference between two internal fixation methods Kaneda and Z-plate in the operation of anterior surgical approach and decompression after thoracolumbar fractures. METHODS: The bio-mechanical structure of the internal fixture, install when operating, complications and time of the operation were compared in the cases by Kaneda and Z-plate. RESULTS: Z-plate method had the following characteristics: reasonable of the bio-mechanical structure; stability after internal fixture being installed; capability of completely propping up the injured centrum and keeping the height of middle-column; simple operation when installing internal fixture and shorter time of operation (1.1 hours, P < 0.05); fewer complications. CONCLUSION: Z-plate is an ideal internal fixation method in the operation of anterior surgical approach after thoracolumbar fractures.