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Background: Developments in minimally invasive surgical techniques (MIS) have sparked debate over the optimal intervention for calcaneal fractures. This meta-analysis compares the extensile lateral approach (ELA) to two MIS techniques; the sinus tarsi approach and percutaneous approaches., Methods: A systematic search was conducted across seven databases for randomised control trials (RCTs). The clinical outcomes were wound complications, functional scores (American Orthopaedic Foot & Ankle Society score, and Maryland Foot Score) and radiological measures (Böhler's and Gissane's angles)., Results: Fourteen RCTs (n = 1367; mean age: 36.3 years; 25.7 % female) were included. MIS significantly reduced wound complications compared to ELA (RR 6.48, 95 %CI 4.03-10.41, p < 0.00001, n = 1380, GRADE: High). Functional scores favoured MIS, and radiological outcomes were equivalent., Conclusions: Both MIS techniques reduce wound complications, improve functional outcomes, and achieve comparable anatomical reduction, making them suitable alternatives to the extensile lateral approach, to significantly improve patient's outcomes., Level of Evidence: Level 1., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A 19-year-old male patient with a history of congenital left oval window defect has had recurrent admissions to a children's hospital for bacterial meningitis since the age of 7. Investigations revealed a left-sided type 1 incomplete partition deformity of the left ear with a congenital oval window defect, leading to communication between the cranium and the middle ear. The patient underwent a left canal wall down mastoidectomy and oval window defect repair, remaining well for 3 years. He experienced two more episodes of bacterial meningitis as he got older, prompting repeated exploratory tympanotomy and repair of the cerebrospinal fluid (CSF) leak after each episode. Recently, he was referred again for recurrent meningitis. Investigations showed a recurrent oval window defect. After undergoing left external ear canal transection, mastoid and middle ear obliteration, and left Eustachian tube obliteration, he remained well without further leaks or meningitis. Congenital oval window defect is rare and may present with recurrent bacterial meningitis secondary to spontaneous CSF leak via the oval window. Radiology plays a crucial role in identifying the source of the CSF leak, facilitating more precise preoperative counseling and surgical intervention.

Background: Early in the COVID-19 pandemic, there was a global shortage of masks. Although mask reprocessing was practiced, no clinical study has assessed systematically the impact of repeated cycles of wear and decontamination on the integrity of N95 filtering facepiece respirators (FFRs)., Methods: We evaluated mask fit assessed by qualitative respirator fit test (QRFT) after each cycle of wear and decontamination, as well as four measures of mask integrity-bacterial filtration efficacy, particle filtration efficacy, differential pressure, and splash resistance through five cycles of wear and decontamination using one of the four modalities (moist heat, steam, ultraviolet-C irradiation, and hydrogen peroxide plasma)., Results: A total of 60.6% (hydrogen peroxide plasma) to 77.5% (moist heat) of the FFRs passed five cycles of wear and decontamination, as assessed by the wearers passing QRFT all five times. Moist heat-decontaminated FFRs retained all technical measures of integrity through all five cycles., Conclusions: This is the first large-scale study to assess systematically the impact (clinically and quantitatively) on N95 FFR integrity of repeated cycles of wearing followed by decontamination. Our results suggest that moist heat is a promising method for decontaminating N95 FFRs. Performing QRFT after every cycle of wear and decontamination ensures wearer safety. Although there is currently no mask shortage, reprocessing may reduce medical waste and improve sustainability., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare, (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Neurodegenerative diseases are critical in the healthcare system as patients suffer from progressive diseases despite currently available drug management. Indeed, the growing ageing population will burden the country's healthcare system and the caretakers. Thus, there is a need for new management that could stop or reverse the progression of neurodegenerative diseases. Stem cells possess a remarkable regenerative potential that has long been investigated to resolve these issues. Some breakthroughs have been achieved thus far to replace the damaged brain cells; however, the procedure's invasiveness has prompted scientists to investigate using stem-cell small extracellular vesicles (sEVs) as a non-invasive cell-free therapy to address the limitations of cell therapy. With the advancement of technology to understand the molecular changes of neurodegenerative diseases, efforts have been made to enrich stem cells' sEVs with miRNAs to increase the therapeutic efficacy of the sEVs. In this article, the pathophysiology of various neurodegenerative diseases is highlighted. The role of miRNAs from sEVs as biomarkers and treatments is also discussed. Lastly, the applications and delivery of stem cells and their miRNA-enriched sEVs for treating neurodegenerative diseases are emphasised and reviewed.

Longus colli tendinitis (LCT) has been described in several case reports, and is likely underdiagnosed due to its non-specific symptoms and self-limiting nature. It usually presents as acute neck pain with retropharyngeal swelling seen on nasoendoscopy and imaging studies. This may lead to unnecessary invasive interventions if physicians are unaware of the disease course. We discuss a case of LCT in a young woman who was treated at our institution, with recommendations on how to identify and treat such cases accurately without overtreatment., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The redeployment of mentors and restrictions on in-person face-to-face mentoring meetings during the COVID-19 pandemic has compromised mentoring efforts in Palliative Medicine (PM). Seeking to address these gaps, we evaluate the notion of a combined novice, peer-, near-peer and e-mentoring (CNEP) and interprofessional team-based mentoring (IPT) program., Methods: A Systematic Evidence Based Approach (SEBA) guided systematic scoping review was carried out to study accounts of CNEP and IPT from articles published between 1st January 2000 and 28th February 2021. To enhance trustworthiness, concurrent thematic and content analysis of articles identified from structured database search using terms relating to interprofessional, virtual and peer or near-peer mentoring in medical education were employed to bring together the key elements within included articles., Results: Fifteen thousand one hundred twenty one abstracts were reviewed, 557 full text articles were evaluated, and 92 articles were included. Four themes and categories were identified and combined using the SEBA's Jigsaw and Funnelling Process to reveal 4 domains - characteristics, mentoring stages, assessment methods, and host organizations. These domains suggest that CNEP's structured virtual and near-peer mentoring process complement IPT's accessible and non-hierarchical approach under the oversight of the host organizations to create a robust mentoring program., Conclusion: This systematic scoping review forwards an evidence-based framework to guide a CNEP-IPT program. At the same time, more research into the training and assessment methods of mentors, near peers and mentees, the dynamics of mentoring interactions and the longitudinal support of the mentoring relationships and programs should be carried out., (© 2022. The Author(s).)

Background: Recognizing that physicians may struggle to achieve knowledge, skills, attitudes and or conduct at one or more stages during their training has highlighted the importance of the 'deliberate practice of improving performance through practising beyond one's comfort level under guidance'. However, variations in physician, program, contextual and healthcare and educational systems complicate efforts to create a consistent approach to remediation. Balancing the inevitable disparities in approaches and settings with the need for continuity and effective oversight of the remediation process, as well as the context and population specific nature of remediation, this review will scrutinise the remediation of physicians in training to better guide the design, structuring and oversight of new remediation programs., Methods: Krishna's Systematic Evidence Based Approach is adopted to guide this Systematic Scoping Review (SSR in SEBA) to enhance the transparency and reproducibility of this review. A structured search for articles on remediation programs for licenced physicians who have completed their pre-registration postings and who are in training positions published between 1st January 1990 and 31st December 2021 in PubMed, Scopus, ERIC, Google Scholar, PsycINFO, ASSIA, HMIC, DARE and Web of Science databases was carried out. The included articles were concurrently thematically and content analysed using SEBA's Split Approach. Similarities in the identified themes and categories were combined in the Jigsaw Perspective and compared with the tabulated summaries of included articles in the Funnelling Process to create the domains that will guide discussions., Results: The research team retrieved 5512 abstracts, reviewed 304 full-text articles and included 101 articles. The domains identified were characteristics, indications, frameworks, domains, enablers and barriers and unique features of remediation in licenced physicians in training programs., Conclusion: Building upon our findings and guided by Hauer et al. approach to remediation and Taylor and Hamdy's Multi-theories Model, we proffer a theoretically grounded 7-stage evidence-based remediation framework to enhance understanding of remediation in licenced physicians in training programs. We believe this framework can guide program design and reframe remediation's role as an integral part of training programs and a source of support and professional, academic, research, interprofessional and personal development., (© 2022. The Author(s).)

Background: Losing a child tragically impacts the well-being and functioning of parents. With these effects extending beyond emotional, physical morbidity and compromising self-perceptions, appropriate, longitudinal, timely and personalised support is key to effective care of bereaved parents. However, in the absence of a comprehensive understanding of parental bereavement, effective support of bereaved parents remains suboptimal. To address this gap, we scrutinise prevailing data on the effects of a child's death, aged 0-12 years, through the lens of the Ring Theory of Personhood (RToP)., Methods: To study prevailing accounts of bereaved parents following the death of a child, we adopt Krishna's Systematic Evidence Based Approach (SEBA) to structure our Systematic Scoping Review (SSR in SEBA)., Results: Three thousand seventy-four abstracts were reviewed, 160 full text articles were evaluated, and 111 articles were included and analysed using thematic and content analysis. Four themes/categories were identified relating to the four rings of the RToP. Findings reveal that static concepts of protective and risk factors for grief are misplaced and that the support of healthcare professionals is key to assisting bereaved parents., Conclusion: In the absence of consistent support of bereaved parents, this study highlights the need for effective training of healthcare professionals, beginning with an appreciation that every aspect of an individual parent's personhood is impacted by the loss of their child. Acknowledging grief as a complex, evolving and personalised process subjected to parental characteristics, settings, context and available support, this SSR in SEBA calls attention to effective nurturing of the relationship between parents and healthcare professionals, and suggests use of the RToP to assess and direct personalised, timely, specific support of parents in evolving conditions. We believe the findings of this review also call for further studies to support healthcare professionals as they journey with bereaved parents., (© 2021. The Author(s).)

The coronavirus disease 2019 (COVID-19) pandemic had caused a severe depletion of the worldwide supply of N95 respirators. The development of methods to effectively decontaminate N95 respirators while maintaining their integrity is crucial for respirator regeneration and reuse. In this study, we systematically evaluated five respirator decontamination methods using vaporized hydrogen peroxide (VHP) or ultraviolet (254 nm wavelength, UVC) radiation. Through testing the bioburden, filtration, fluid resistance, and fit (shape) of the decontaminated respirators, we found that the decontamination methods using BioQuell VHP, custom VHP container, Steris VHP, and Sterrad VHP effectively inactivated Cardiovirus (3-log 10 reduction) and bacteria (6-log 10 reduction) without compromising the respirator integrity after 2-15 cycles. Hope UVC system was capable of inactivating Cardiovirus (3-log 10 reduction) but exhibited relatively poorer bactericidal activity. These methods are capable of decontaminating 10-1000 respirators per batch with varied decontamination times (10-200 min). Our findings show that N95 respirators treated by the previously mentioned decontamination methods are safe and effective for reuse by industry, laboratories, and hospitals., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background: Amidst expanding roles in education and policy making, questions have been raised about the ability of Clinical Ethics Committees (CEC) s to carry out effective ethics consultations (CECons). However recent reviews of CECs suggest that there is no uniformity to CECons and no effective means of assessing the quality of CECons. To address this gap a systematic scoping review of prevailing tools used to assess CECons was performed to foreground and guide the design of a tool to evaluate the quality of CECons., Methods: Guided by Levac et al's (2010) methodological framework for conducting scoping reviews, the research team performed independent literature reviews of accounts of assessments of CECons published in six databases. The included articles were independently analyzed using content and thematic analysis to enhance the validity of the findings., Results: Nine thousand sixty-six abstracts were identified, 617 full-text articles were reviewed, 104 articles were analyzed and four themes were identified - the purpose of the CECons evaluation, the various domains assessed, the methods of assessment used and the long-term impact of these evaluations., Conclusion: This review found prevailing assessments of CECons to be piecemeal due to variable goals, contextual factors and practical limitations. The diversity in domains assessed and tools used foregrounds the lack of minimum standards upheld to ensure baseline efficacy. To advance a contextually appropriate, culturally sensitive, program specific assessment tool to assess CECons, clear structural and competency guidelines must be established in the curation of CECons programs, to evaluate their true efficacy and maintain clinical, legal and ethical standards.

Introduction: Professionalism is an evolving, socioculturally informed multidimensional construct that influences doctor-patient relationships, patient satisfaction and care outcomes. However, despite its clinical significance there is little consistency in how professionalism is nurtured amongst medical students. To address this gap a systemic scoping review of nurturing professionalism in medical schools, is proposed. Methods: Levac's framework and the PRISMA-P 2015 checklist underpinned a 6-stage systematic review protocol. Concurrent use of Braun and Clarke's approach to thematic analysis and directed content analysis was used to identify the key elements in nurturing professionalism. Results: 13921 abstracts were identified from six databases, 854 full-text articles reviewed, and 162 full-text included articles were included. The 4 themes identified through thematic analysis are consistent with findings of the directed content analysis. These were the definition of professionalism, the approaches, content, barriers and enablers to teaching professionalism. Conclusion: Informed by a viable definition of professionalism and clear milestones nurturing professionalism nurturing professionalism begins with culturally appropriate training in clinical competence, humanistic qualities and reflective capacity. This process requires effective evaluations of professional identity formation, and the impact of the learning environment underlining the need for longitudinal assessments of the training process.

Mentoring is suffering from a shortage of trained mentors which compromise the efficacy of novice mentoring or mentoring between a senior clinician and a junior clinician. E-mentoring is proposed as a means of supplementing this dominant form of mentoring in medicine by providing accessible, timely and longitudinal support for mentees. However, with little is known about e-mentoring nor its role in a blended mentoring approach, a systematic scoping review is proposed to evaluate these gaps in understanding in order to better understand e-mentoring and assess the viability of employing e-mentoring practice to support novice mentoring. Using Arksey and O'Malley's (Int J Soc Res Methodol 8(1):19-32, 2005) approach, 5 reviewers carried out independent literature reviews of e-mentoring as an adjuvant to novice mentoring in PubMed, Embase, PsycINFO, ERIC, Cochrane Database of Systematic Reviews, Google Scholar, Scopus, GreyLit, OpenGrey, and Web of Science databases. Braun and Clarke's (Qual Res Psychol 3(2):77-101, 2006) thematic analysis approach was used to thematically analyse accounts of e-mentoring across different settings. 6557 abstracts were identified, 109 full text articles were reviewed, and 18 articles were included and thematically analysed. The themes identified include definitions, role, stages, processes, platforms, evaluation, and relationships in e-mentoring. The themes identified provide a clinically relevant definition of e-mentoring, and in highlighting the similarities in the phases of novice and e-mentoring reaffirms the validity of a blended approach as a means of addressing shortfalls in mentoring in medicine.

Responsive delivery of anticancer proteins into cells is an emerging field in biological therapeutics. Currently, the delivery of proteins is highly compromised by multiple successive physiological barriers that reduce the therapeutic efficacy. Hence, there is a need to design a robust and sustainable nanocarrier to provide suitable protection of proteins and overcome the physiological barriers for better cellular accumulation. In this work, polyethylenimine (PEI) cross-linked by oxaliplatin(IV) prodrug (oxliPt(IV)) was used to fabricate a redox-responsive nanocomplex (PEI-oxliPt(IV)@RNBC/GOD) for the delivery of a reactive oxygen species-cleavable, reversibly caged RNase A protein (i.e., RNase A nitrophenylboronic conjugate, RNBC) and glucose oxidase (GOD) in order to realize efficient cancer treatment. The generation of hydrogen peroxide by GOD can uncage and restore the enzymatic activity of RNBC. On account of the responsiveness of the nanocomplex to highly reducing cellular environment, it would dissociate and release the protein and active oxaliplatin drug, causing cell death by both catalyzing RNA degradation and inhibiting DNA synthesis. As assessed by the RNA degradation assay, the activity of the encapsulated RNBC was recovered by the catalytic production of hydrogen peroxide from GOD and glucose substrate overexpressed in cancer cells. Monitoring of the changes in nanoparticle size confirmed that the nanocomplex could dissociate in the reducing environment, with the release of active oxaliplatin drug and protein. Confocal laser scanning microscopy (CLSM) and flow cytometry analysis revealed highly efficient accumulation of the nanocomplex as compared to free native proteins. In vitro cytotoxicity experiments using 4T1 cancer cells showed ∼80% cell killing efficacy, with highly efficient apoptosis induction. Assisted by the cationic polymeric carrier, it was evident from CLSM images that intracellular delivery of the therapeutic protein significantly depleted the RNA level. Thus, this work provides a promising platform for the delivery of therapeutic proteins and chemotherapeutic drugs for efficient cancer treatment.

Tumor hypoxia compromises the therapeutic efficiency of photodynamic therapy (PDT) as the local oxygen concentration plays an important role in the generation of cytotoxic singlet oxygen ( 1 O 2 ). Herein, a versatile mesoporous nanoenzyme (NE) derived from metal-organic frameworks (MOFs) is presented for in situ generation of endogenous O 2 to enhance the PDT efficacy under bioimaging guidance. The mesoporous NE is constructed by first coating a manganese-based MOFs with mesoporous silica, followed by a facile annealing process under the ambient atmosphere. After removing the mesoporous silica shell and post-modifying with polydopamine and poly(ethylene glycol) for improving the biocompatibility, the obtained mesoporous NE is loaded with chlorin e6 (Ce6), a commonly used photosensitizer in PDT, with a high loading capacity. Upon the O 2 generation through the catalytic reaction between the catalytic amount NE and the endogenous H 2 O 2 , the hypoxic tumor microenvironment is relieved. Thus, Ce6-loaded NE serves as a H 2 O 2 -activated oxygen supplier to increase the local O 2 concentration for significantly enhanced antitumor PDT efficacy in vitro and in vivo. In addition, the NE also shows T 2 -weighted magnetic resonance imaging ability for its in vivo tracking. This work presents an interesting biomedical use of MOF-derived mesoporous NE as a multifunctional theranostic agent in cancer therapy., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Uncontrolled cancer cell proliferation, insufficient blood flow, and inadequate endogenous oxygen lead to hypoxia in tumor tissues. Herein, a unique type of hypoxia-responsive human serum albumin (HSA)-based nanosystem (HCHOA) is reported, prepared by cross-linking the hypoxia-sensitive azobenzene group between photosensitizer chlorin e6 (Ce6)-conjugated HSA (HC) and oxaliplatin prodrug-conjugated HSA (HO). The HCHOA nanosystem is stable under normal oxygen partial pressure with a size of 100-150 nm. When exposed to the hypoxic tumor microenvironment, the nanosystem can quickly dissociate into ultrasmall HC and HO therapeutic nanoparticles with a diameter smaller than 10 nm, significantly enabling their enhanced intratumoral penetration. After the dissociation, the quenched fluorescence of Ce6 in the produced HC nanoparticles can be recovered for bioimaging. At the same time, the production of singlet oxygen is increased because of the enhancement in the photoactivity of the photosensitizer. On account of these improvements, combined photodynamic therapy and chemotherapy is realized to display superior antitumor efficacy in vivo. Based on this simple strategy, it is possible to achieve the dissociation of hypoxic-responsive nanosystem to enhance the tumor penetration and therapeutic effect., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Recently, we found that self-organization of hydroxyapatite (HAp) with poly(acrylic acid) (PAA) leads to the formation of liquid-crystalline (LC) nanorod hybrids that form aligned films and show stimuli-responsive properties. Here, we demonstrate that these biocompatible HAp/PAA hybrid nanorods represent a platform technology as drug nanocarriers for photodynamic cancer therapy and as bioscaffolds for the control of cellular alignment and growth. To use hybrid nanorods as a drug nanocarrier, we introduced methylene blue (MB), a typical photosensitizer for photodynamic therapy, into the PAA nanolayer covering the surface of the HAp nanocrystals through electrostatic interactions. The stable MB-loaded HAp/PAA hybrid nanorods efficiently produced singlet oxygen from MB upon light irradiation and showed remarkable photodynamic therapeutic effects in cancer cells. Moreover, taking advantage of the mechanically responsive LC alignment properties of the HAp/PAA hybrid nanorods, macroscopically oriented bioscaffolds were prepared through a spin-coating process. The cells cultured on the oriented scaffolds showed cellular alignment and elongation along the oriented direction of the hybrid nanorods. The HAp/PAA hybrid nanorods demonstrate potential in drug delivery and tissue engineering. These unique LC HAp/PAA hybrid nanorods have significant potential as a platform for the development of various types of biomaterial.

Nanomedicine has emerged as a promising strategy for effective cancer treatment. A useful approach is to develop carrier-free nanodrugs via a facile supramolecular self-assembly process. To achieve high therapeutic effect, integrating photodynamic therapy with chemotherapy has been sought after. In this work, we designed a nanocarrier (PEG-Por-CD: oxliPt(IV)-ada) assembled with oxaliplatin prodrug (oxliPt(IV)-ada) and porphyrin photosensitizer (PEG-Por-CD) through host-guest interaction to achieve stimulus-responsive combination therapy. Contributed by excellent spatial control of the binding ratio between host and guest molecules, porphyrin and oxaliplatin were separately modified with β-cyclodextrin and adamantane to prepare the amphiphilic host-guest complex for subsequent self-assembly into therapeutic nanoparticles. The obtained PEG-Por-CD: oxliPt(IV)-ada nanoparticles exhibited good colloidal stability with an average hydrodynamic size of 164 nm while undergoing the disassembly under reductive environment to release active therapeutic species. Confocal imaging demonstrated the ability of PEG-Por-CD: oxliPt(IV)-ada to effectively accumulate in the cells and produce reactive oxygen species in vitro upon 630 nm light irradiation. As compared with the monotherapy, the PEG-Por-CD: oxliPt(IV)-ada nanoparticles exhibited 3-fold enhanced cytotoxicity and 2-fold increase in the apoptosis. In vivo experiments using 4T1 tumor-bearing mice confirmed that the nanoparticles were efficient in suppressing the tumor growth without eliciting systemic toxicity. The present self-delivery nanosystem constructed from the self-assembly approach not only allows precise control over the drug and photosensitizer loading ratio but also eliminates systemic toxicity concern of the drug carriers, providing a solution for further development of combinational cancer treatment.

Photodynamic therapy (PDT) as a treatment method has many advantages such as minimal invasiveness, repeatable dosage, and low systemic toxicity. Issues with conventional PDT agents include the limited availability of endogenous oxygen and difficulty in accumulation at the tumor site, which has hindered the successful treatment of tumors. Herein, we developed catalase-encapsulated hyaluronic-acid-based nanoparticles loaded with adamantane-modified photosensitizer for enhanced PDT of solid tumors. Chlorin e6 (Ce6) as the photosensitizer was modified with adamantane to yield adamantane-modified Ce6 (aCe6). The obtained nanosystem (HA-CAT@aCe6) could target overly expressed CD44 receptors on cancer cells, supplying oxygen by converting endogenous hydrogen peroxide (H 2 O 2 ) to oxygen, and improving PDT efficacy upon light irradiation. HA-CAT@aCe6 nanoparticles showed high colloidal stability and monodispersity in aqueous solution. The uptake and targeting property of HA-CAT@aCe6 were demonstrated by confocal microscopy and flow cytometry in the MDA-MB-231 cell line possessing overly expressed CD44 receptors. The encapsulated catalase was able to decompose the endogenous H 2 O 2 to generate O 2 in situ for relieving hypoxia in cells incubated under hypoxic conditions. Cell viability assays indicated that HA-CAT@aCe6 possessed minimal cytotoxicity in the dark, while presenting high cellular toxicity under 660 nm light irradiation at normoxic conditions. As a result of the catalase capability in relieving hypoxia, HA-CAT@aCe6 also exhibited high cellular cytotoxicity under hypoxic condition. In vivo experiments revealed selective tumor accumulation of HA-CAT@aCe6 in MDA-MB-231 tumor bearing nude mice. Significant tumor regression was observed after intravenous injection of HA-CAT@aCe6 under light irradiation in comparison to the control system without loading catalase. Thus, HA-CAT@aCe6 demonstrated a great potential in overcoming hypoxia for targeted PDT.

Topical treatment using photodynamic therapy (PDT) for many types of skin cancers has largely been limited by the inability of existing photosensitizers to penetrate into the deep skin tissue. To overcome these problems, we developed a mesoporous nanovehicle with dual loading of photosensitizers and clinically relevant drugs for combination therapy, while utilizing microneedle technology to facilitate their penetration into deep skin tissue. Sub-50 nm photodynamically active mesoporous organosilica nanoparticles were synthesized with photosensitizers covalently bonded to the silica matrix, which dramatically increased the quantum yield and photostability of these photosensitizers. The mesopores of the nanoparticles were further loaded with small-molecule inhibitors, i. e., dabrafenib and trametinib, that target the hyperactive mitogen-activated protein kinase (MAPK) pathway for melanoma treatment. As-prepared empty nanovehicle was cytocompatible with normal skin cells in the dark, while NIR-irradiated drug-loaded nanovehicle showed a synergistic killing effect on skin cancer cells mainly through reactive oxygen species and caspase-activated apoptosis. The nanovehicle could significantly inhibit the proliferation of tumor cells in a 3D spheroid model in vitro. Porcine skin fluorescence imaging demonstrated that microneedles could facilitate the penetration of nanovehicle across the epidermis layer of skin to reach deep-seated melanoma sites. Tumor regression studies in a xenografted melanoma mouse model confirmed superior therapeutic efficacy of the nanovehicle through combinational PDT and targeted therapy.

A redox-responsive supramolecular nanocarrier was constructed from the self-assembly of spermine modified cyclodextrin and oxaliplatin prodrug. The nanocarrier could preferentially accumulate in polyamine transporter over-expressing HCT116 cells, releasing drugs under a reducing intracellular environment to maximize anticancer treatment.

Ultralong room temperature phosphorescence (URTP) emitted from pure amorphous organic molecules is very rare. Although a few crystalline organic molecules could realize URTP with long lifetimes (>100 ms), practical applications of these crystalline organic phosphors are still challenging because the formation and maintenance of high-quality crystals are very difficult and complicated. Herein, we present a rational design for minimizing the vibrational dissipation of pure amorphous organic molecules to achieve URTP. By using this strategy, a series of URTP films with long lifetimes and high phosphorescent quantum yields (up to 0.75 s and 11.23%, respectively) were obtained from amorphous organic phosphors without visible fluorescence and phosphorescence under ambient conditions. On the basis of the unique features of URTP films, a new green screen printing technology without using any ink was developed toward confidential information encryption and decryption. This work presents a breakthrough strategy in applying amorphous organic materials for URTP.

In this study, a reduction-sensitive supramolecular polymeric drug delivery system was developed for combinational photothermal-chemotherapy of cancer. The multifunctional system was self-assembled by specific host-guest interactions between hydrophilic β-cyclodextrin functionalized hyaluronic acid and adamantane linked camptothecin/dye conjugate, where a near-infrared (NIR) absorbing dye IR825 was loaded. The hydrophilic hyaluronic acid shell endows the assembly with excellent colloidal stability and biocompatibility. The embedded disulfide bond in the camptothecin/dye conjugate was cleaved under reducing environment, leading to the release of the conjugated drug and the recovery of fluorescence emission. Meanwhile, the dye IR825 could efficiently transfer the absorbed light into local heat, making the nanoplatform an effective system for photothermal therapy. As evident by confocal microscopy images, the nanoplatform was quickly internalized by HeLa, MCF-7, and U14 cancer cells and released drug molecules inside the cells. In vitro cell viability assays confirmed that the cancer cells were efficiently killed by the treatment of the nanoplatform under NIR light irradiation. Significant tumor regression was also observed in the tumor-bearing mice upon the administration of the nanoplatform through combinational photothermal-chemotherapy therapy. Hence, this nanoplatform presented a great potential in site-specific combined photothermal-chemotherapy of tumor., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: In this study, we report the design, development and evaluation of a hollow drug delivery nanoplatform for cancer therapy in vitro and in vivo . This composite nanosystem was prepared by modifying hollow mesoporous silica nanoparticles (HMSNs) with transferrin (Tf) targeting moieties via redox-liable linkage, and was capable of delivering therapeutic cargos (doxorubicin) specifically to the tumor site and subsequently releasing them in an on-demand manner. Moreover, the Tf corona could simultaneously reduce the inflammatory response after intravenous administration in vivo . Methods: Nanostructural morphology of the drug delivery system was observed by scanning electron microscope and transmission electron microscope. The preparation process was monitored primarily using Fourier-transform infrared spectroscopy, dynamic light scattering, nitrogen adsorption/desorption isotherm, and thermogravimetric analysis. The release profile in solution was monitored by fluorescence spectroscopy. In vitro drug delivery efficacy was evaluated on MDA-MB-231 breast cancer cell line using confocal laser scanning microscopy, MTT assay and flow cytometry. In vitro inflammatory response was evaluated on RAW264.7 macrophage cells. In vivo therapeutic experiments were carried out using in situ mouse breast cancer models. Results: The experimental results evidently demonstrate that the developed nanocarrier could effectively deliver anticancer drugs to the tumor site in a targeted manner and release them in response to the elevated glutathione level inside tumor cells, resulting in improved anticancer efficacy both in vitro and in vivo . Moreover, the Tf conjugation significantly ameliorated the inflammatory reaction triggered by the administration of the nanocarrier. Conclusions: This manuscript demonstrated that the Tf-conjugated HMSNs could enhance the delivery efficiency of anticancer drugs, while simultaneously alleviating the adverse side effects. The current study presents a promising integrated delivery system toward effective and safe cancer treatment., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Developing multifunctional hybrid nanosystems for controlled drug delivery is a challenging task. In this work, we prepared hierarchical core-shell nanoparticles (ZnO-DOX@ZIF-8) composed of mesoporous ZnO core and microporous ZIF-8 shell, in which the core serves as the drug storage reservoir for the loading of anticancer drug doxorubicin (DOX) and the shell could be used to prevent premature release of loaded drug at physiological environment. The mesoporous ZnO nanoparticles were first prepared, followed by DOX drug loading. Such ZnO nanoparticles were then employed as the zinc source to react with 2-methylimidazole for the formation of ZnO-DOX@ZIF-8 core-shell nanoparticles. The core-shell nanoparticles exhibit good dispersibility and stability as well as pH-responsive drug release property. While only up to 20% of loaded DOX was released in the buffer of pH 7.4, over 80% of DOX was released in the buffer of pH 5.5 because of the decomposition of the ZIF-8 shell as well as the dissolution of the ZnO core under acidic conditions. The confocal microscopy studies show that the core-shell nanoparticles could be efficiently internalized by cancer cells, and the loaded DOX in the nanoparticles could be successfully released under acidic intracellular environment. The in vitro cytotoxicity measurements demonstrate that the core-shell nanoparticles free of drug exhibit a significant cytotoxicity when the concentration was above 25 μg/mL on account of the production of reactive oxygen species. The reactive oxygen species are only generated in acidic condition, which could combine with DOX for a synergistic cancer treatment with satisfactory therapeutic efficacy. On the other hand, the nanoparticles were stable and nontoxic in physiological environment. Thus, the ZnO-DOX@ZIF-8 core-shell nanoparticles are a promising pH-responsive drug delivery system for the cancer therapy.

Discriminative detection of glutathione (GSH) from cysteine/homocysteine (Cys/Hcy) is achieved through two emission channel analysis using a stable, highly sensitive, and selective near-infrared fluorescent probe that bears 7-nitrobenzo-2-oxa-1,3-diazole and aza-BODIPY units. The probe was successfully applied for simultaneous determination of GSH and Cys/Hcy in living cells.

In recent years, there has been a considerable research focus on integrating cancer cell imaging and therapeutic functions into single nanoscale platforms for better treatment of cancer. This task could often be achieved by incorporating multiple components into a hybrid nanosystem. In this minireview, we highlight different types of silica-based hybrid nanosystems and their recent applications as integrated multifunctional platforms for cancer imaging and treatment. The discussions are divided into several sections focusing on various types of materials employed to integrate with silica, which include silica-metallic nanoparticle based hybrid nanocarriers, silica-gold nanoparticle based hybrid nanocarriers, silica-quantum dot based hybrid nanocarriers, silica-upconversion nanoparticle based hybrid nanocarriers, silica-carbon based hybrid nanocarriers, and organosilica nanocarriers. Therapeutic agents loaded in such hybrids include chemodrugs, proteins, DNA/RNA and photosensitizers. For targeted delivery into tumor sites, targeting ligands such as antibodies, peptides, aptamers, and other small molecules are grafted on the surface of the nanocarriers. At the end of the review, a brief summary and research outlook are presented. This minireview aims to provide a quick update of recent research achievements in the field.

Two porous covalent organic frameworks (COFs) with good biocompatibility were employed as drug nanocarriers, where three different drugs were loaded for subsequent drug release in vitro. The present work demonstrates that COFs are applicable in drug delivery for therapeutic applications.

A direct and facile method for micro-landscaping of Ag nanoparticles on reduced graphene oxide (rGO) is presented. This method employs a focused laser beam to achieve local reduction of Ag(+) ions to Ag NPs by laser irradiation on a GO film that is submerged in AgNO3 solution. Using this method, the Ag nanoparticles can be directly anchored on a rGO film, creating a microlandscape of Ag nanoparticles on the rGO film. In addition, varying the intensity of the laser beam can control the shapes, sizes and distributions of Ag nanoparticles. The resulting hybrid materials exhibit surface enhanced Raman scattering of up to 16 times depending on the size and number density of silver nanoparticles. In addition, the hybrid Ag-rGO material shows superior photoresponse when compared to rGO.

Over the past few years, various representation systems which sparsely approximate functions governed by anisotropic features, such as edges in images, have been proposed. Alongside the theoretical development of these systems, algorithmic realizations of the associated transforms are provided. However, one of the most common shortcomings of these frameworks is the lack of providing a unified treatment of the continuum and digital world, i.e., allowing a digital theory to be a natural digitization of the continuum theory. In this paper, we introduce a new shearlet transform associated with a nonseparable shearlet generator, which improves the directional selectivity of previous shearlet transforms. Our approach is based on a discrete framework, which allows a faithful digitization of the continuum domain directional transform based on compactly supported shearlets introduced as means to sparsely encode anisotropic singularities of multivariate data. We show numerical experiments demonstrating the potential of our new shearlet transform in 2D and 3D image processing applications.

It is now widely acknowledged that analyzing the intrinsic geometrical features of the underlying image is essential in many applications including image processing. In order to achieve this, several directional image representation schemes have been proposed. In this paper, we develop the discrete shearlet transform (DST) which provides efficient multiscale directional representation and show that the implementation of the transform is built in the discrete framework based on a multiresolution analysis (MRA). We assess the performance of the DST in image denoising and approximation applications. In image approximations, our approximation scheme using the DST outperforms the discrete wavelet transform (DWT) while the computational cost of our scheme is comparable to the DWT. Also, in image denoising, the DST compares favorably with other existing transforms in the literature.