PD-1/CD80+ small extracellular vesicles from immunocytes induce cold tumours featured with enhanced adaptive immunosuppression.

Only a minority of cancer patients benefit from immune checkpoint blockade therapy. Sophisticated cross-talk among different immune checkpoint pathways as well as interaction pattern of immune checkpoint molecules carried on circulating small extracellular vesicles (sEV) might contribute to the low response rate. Here we demonstrate that PD-1 and CD80 carried on immunocyte-derived sEVs (I-sEV) induce an adaptive redistribution of PD-L1 in tumour cells. The resulting decreased cell membrane PD-L1 expression and increased sEV PD-L1 secretion into the circulation contribute to systemic immunosuppression. PD-1/CD80+ I-sEVs also induce downregulation of adhesion- and antigen presentation-related molecules on tumour cells and impaired immune cell infiltration, thereby converting tumours to an immunologically cold phenotype. Moreover, synchronous analysis of multiple checkpoint molecules, including PD-1, CD80 and PD-L1, on circulating sEVs distinguishes clinical responders from those patients who poorly respond to anti-PD-1 treatment. Altogether, our study shows that sEVs carry multiple inhibitory immune checkpoints proteins, which form a potentially targetable adaptive loop to suppress antitumour immunity.

Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases: A case report.

BACKGROUND: Small cell lung cancer (SCLC) is a common and aggressive subtype of lung cancer. It is characterized by rapid growth and a high mortality rate. Approximately 10% of patients with SCLC present with brain metastases at the time of diagnosis, which is associated with a median survival of 5 mo. This study aimed to summarize the effect of bevacizumab on the progression-free survival (PFS) and overall survival of patients with brain metastasis of SCLC. CASE SUMMARY: A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks. The patient was diagnosed with limited-stage SCLC. He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo. CONCLUSION: The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

A tumor-targeted and enzyme-responsive gold nanorod-based nanoplatform with facilitated endo-lysosomal escape for synergetic photothermal therapy and protein therapy.

To tackle the obstacles related to tumor targeting and overcome the limitations of single treatment models, we have developed a nanoplatform that is both tumor-targeted and enzyme-responsive. This nanoplatform integrates photothermal gold nanorods (AuNRs) and protein drugs into a single system. This nanosystem, known as AuNRs@HA-mPEG-Deta-LA, was fabricated by modifying gold nanorods (AuNRs) with a polymeric ligand called hyaluronic acid-grafted-(mPEG/diethylenetriamine-conjugated-lipoic acid). The purpose of this fabrication was to load cytochrome c (CC) and utilize it for the synergetic protein-photothermal therapy of cancer. The resulting nanoplatform exhibited a high efficiency in loading proteins and demonstrated excellent stability in different biological environments. Additionally, CC-loaded AuNRs@HA-mPEG-Deta-LA not only enabled localized hyperthermia for photothermal therapy (PTT) with laser irradiation but also facilitated the release of CC under the action of hyaluronidase, an enzyme known to be overexpressed in tumor cells. The confocal imaging results demonstrated that the presence of a specific polymeric ligand on this nanoparticle enhances the internalization of CD44-positive cancer cells, accelerates endo/lysosomal escape, and facilitates the controlled release of CC within the cells. Furthermore, the results of the MTT assay also showed that AuNRs@HA-mPEG-Deta-LA as a protein nanocarrier demonstrated excellent biocompatibility. Importantly, this synergistic therapeutic strategy effectively induced apoptosis in A549 cancer cells by increasing the intracellular concentration of CC and utilizing the photothermal conversion of AuNRs, which was observed to be more effective compared to using only protein therapy or PTT. Therefore, this study showcased a nanoplatform based on AuNRs that has great potential for tumor-targeted protein delivery in combination with PTT in cancer treatment.

Solitary intraosseous neurofibroma in the mandible mimicking a cystic lesion: A case report and review of literature.

BACKGROUND: Neurofibromas are benign tumors of a neurogenic origin. If these tumors occur without any other signs of neurofibromatosis, they are classified as isolated neurofibromas. Neurofibromas in the oral cavity mostly occur within soft tissues, indicating that solitary intraosseous neurofibromas in the mandible are rare. Due to the absence of specific clinical manifestations, early diagnosis and treatment of these tumors are difficult to achieve. CASE SUMMARY: A 37-year-old female patient visited our hospital due to numbness and swelling of the gums in the right lower molar area that had persisted for half a month. The patient's overall condition and intraoral examination revealed no significant abnormalities. She was initially diagnosed with a cystic lesion in the right mandible. However, after a more thorough examination, the final pathological diagnosis was confirmed to be neurofibroma. Complete tumor resection and partial removal of the right inferior alveolar nerve were performed. As of writing this report, there have been no signs of tumor recurrence for nine months following the surgery. CONCLUSION: This case report discusses the key features that are useful for differentiating solitary intraosseous neurofibromas from other cystic lesions.

Hyperprogression after anti-programmed death-1 therapy in a patient with urothelial bladder carcinoma: A case report.

BACKGROUND: Immune checkpoint inhibitors, including programmed death-ligand 1 (PD-L1) and programmed death-1 (PD-1) have recently been approved to treat locally advanced and metastatic urothelial carcinoma (UC). However, some patients experience rapid tumor progression rather than any clinical benefit from anti-PD-L1/PD-1 therapy. CASE SUMMARY: A 73-year-old woman with bladder UC showed the progression of multiple metastases after surgery and chemotherapy for over 12 mo. The patient could not tolerate further chemotherapy. Next-generation sequencing was performed, and the results indicated that the tumor mutational burden was 6.4 mutations/Mb. The patient received the anti-PD-L1 agent toripalimab combined with albumin-bound paclitaxel. Compared with the baseline staging before immunotherapy, the patient had a treatment failure time of < 2 mo, an increase in tumor burden of > 50%, and a > 2-fold increase in progression, indicating hyperprogression. CONCLUSION: Selecting patients most likely to respond to treatment with immunotherapeutic agents remains challenging. For older patients with advanced UC who have already exhausted multi-line chemotherapy options, immunotherapy should be used prudently if no effective biomarker is available. Further studies are required to clarify the causes and mechanisms of hyperprogression.

Oxygen-Generating Organic/Inorganic Self-Assembled Nanocolloids for Tumor-Activated Dual-Model Imaging-Guided Photodynamic Therapy.

Tumor phototheranostics is usually compromised by the hypoxic tumor microenvironment and poor theranostic efficiency. The interplay between organic polymers and inorganic nanoparticles in novel nanocomposites has proven to be advantageous, overcoming previous limitations and harnessing their full potential through activation via the tumor microenvironment. This study successfully fabricated hypoxia-activated nanocolloids called HOISNDs through a process of self-assembly involving superparamagnetic iron oxide nanoparticles (SPIONs) and an organic polymer ligand called tetrakis(4-carboxyphenyl) porphyrin (TCPP)-engineered organic polymer ligand [methoxy poly(ethyleneglycol)-block-poly(dopamine-ethylenediamine-conjugated-4-nitrobenzyl chloroformate)-l-glutamate, mPEG-b-P(Dopa-EDA-co-NBCF)LG-TCPP)]. The SPIONs act as an oxygen generator to overcome the challenges posed by hypoxic tumors and enable the use of hypoxic-activatable MR/fluorescence dual-modal imaging-guided photodynamic therapy (PDT). The colloid stability of these HOISNDs proved to be exceptional in diverse biomimetic environments. Furthermore, they not only augment T2-weighted contrast capability as an MRI contrast agent but also function as an oxygen-producing device to amplify the generation and release of reactive oxygen species (ROS). The HOISNDs can significantly target to tumor sites through the enhanced permeability and retention (EPR) effect with prolonged blood circulation time and subsequently are effectively endocytosed into a hypoxic intracellular environment that "turn on" the imaging function and photodynamic activity. Moreover, HOISNDs possess the ability to effectively decompose naturally occurring H2O2 into oxygen (O2) within the tumor utilizing the Fenton reaction. This method can mitigate the impact of hypoxia on oxygen-dependent PDT. The outcomes of in vivo diagnostic and therapeutic evaluations indicated that HOISNDs are a highly promising tool for dual-model imaging-guided cancer theranosis by ameliorating hypoxic conditions and augmenting PDT efficiency.

Dual-targeting multifunctional hyaluronic acid ligand-capped gold nanorods with enhanced endo-lysosomal escape ability for synergetic photodynamic-photothermal therapy of cancer.

Au nanorods (AuNRs) have attracted considerable interest as drug delivery systems because of their enhanced cell internalization and stronger drug-loading ability. In addition, the incorporation of photodynamic therapy (PDT) and photothermal therapy (PTT) into one nanosystem presents great promise to defect multiple drawbacks in cancer therapy. Herein, we fabricated a multifunctional and dual-targeting nanoplatform based on hyaluronic acid-grafted-(mPEG/triethylenetetramine-conjugated-lipoic acid/tetra(4-carboxyphenyl)porphyrin/folic acid) polymer ligand capped AuNRs (AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA)) for combined photodynamic-photothermal therapy of cancer. The prepared nanoparticles displayed high TCPP loading capacity and excellent stability in different biological media. Furthermore, AuNRs@HA-g-(mPEG/Teta-co-(LA/TCPP/FA)) not only could produce a localized hyperthermia to conduct PTT, but also generate cytotoxic singlet oxygen (1 O2 ) to perform PDT under laser irradiation. Confocal imaging results disclosed that this nanoparticle endowing the specific function of polymeric ligand could enhance cellular uptake, accelerate endo/lysosomal escape, as well as produce higher reactive oxygen species. Importantly, this combination therapy strategy could also induce higher anticancer potential than PDT or PTT only against MCF-7 tumor cells in vitro. Therefore, this work presented an AuNRs-based therapeutic nanoplatform with great potential in dual-targeting and photo-induced combination therapy of cancer.

CD44-mediated tumor homing of hyaluronic acid nanogels for hypoxia-activated photodynamic therapy against tumor.

In this study, unique hypoxia-activated hyaluronic acid nanogels (HANGs) were reported for CD44-targeted delivery of photosensitizers (chlorin e6, Ce6) for diagnostic imaging and photodynamic therapy (PDT) of cancers. Through the use of a hypoxia-responsive cross-linker (AZO-CDI), the HANGs were prepared by chemically cross-linking primary amine groups-functionalized hyaluronic acid (HA). Under normoxic condition, fluorescence of Ce6 conjugated on the HANGs was highly quenched, and level of reactive oxygen species (ROS) generated from the HANGs was rather low after laser irradiation. However, under hypoxic condition, the HANGs underwent rapid disassociation, and fluorescence of Ce6 conjugated on the HANGs was recovered, triggering high-level singlet oxygen generation after laser irradiation. Due to the presence of HA, the HANGs showed much higher cellular uptake by CD44-positive cancer cells (A549 cells) than that by CD44-negative cancer cells (HepG2 cells). In addition, the HANGs could generate higher level of ROS in A549 cells because of improved cancer cell uptake. This excellent tumor-targeting and singlet oxygen-generating ability of the HANGs was favorable to hypoxia-activated PDT of CD44-positive cancers with significant inhibition of tumor growth within the whole treatment period. Taken together, the HANGs are safe and effective tools in treating CD44-positive cancers.

Clinicopathological and immunological features of new onset kidney disease: a rare event after SARS-CoV-2 vaccination.

The onset of various kidney diseases has been reported after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, detailed clinical and pathological features are lacking. We screened and analyzed patients with newly diagnosed kidney diseases after inactivated SARS-CoV-2 vaccination in Peking University First Hospital from January 2021 to August 2021, and compared them with the reported cases in the literature. We obtained samples of blood, urine and renal biopsy tissues. Clinical and laboratory information, as well as light microscopy, immunostaining and ultrastructural observations, were described. The SARS-CoV-2 spike protein and nucleoprotein were stained using the immunofluorescence technique in the kidney biopsy samples. SARS-CoV-2 specific antibodies were tested using magnetic particle chemiluminescence immunoassay. The study group included 17 patients with a range of conditions including immune-complex-mediated kidney diseases (IgA nephropathy, membranous nephropathy and lupus nephritis), podocytopathy (minimal change disease and focal segmental glomerulosclerosis) and others (antineutrophil-cytoplasmic-antibody-associated vasculitis, anti-glomerular basement membrane nephritis, acute tubulointerstitial nephritis and thrombotic microangiopathy). Seven patients (41.18%) developed renal disease after the first dose and ten (58.82%) after the second dose. The kidney disease spectrum as well as clinicopathological features are similar across different types of SARS-CoV-2 vaccines. We found no definitive evidence of SARS-CoV-2 spike protein or nucleoprotein deposition in the kidney biopsy samples. Seropositive markers implicated abnormal immune responses in predisposed individuals. Treatment and follow-up (median = 86 days) showed that biopsy diagnosis informed treatment and prognosis in all patients. In conclusion, we observed various kidney diseases following SARS-CoV-2 vaccine administration, which show a high consistency across different types of SARS-CoV-2 vaccines. Our findings provide evidence against direct vaccine protein deposition as the major pathomechanism, but implicate abnormal immune responses in predisposed individuals. These findings expand our understanding of SARS-CoV-2 vaccine renal safety.

Factors associated with follow-up attendance of patients with oral squamous cell carcinoma: A retrospective cohort study.

BACKGROUND: This study examined the postoperative follow-up attendance of oral squamous cell carcinoma (OSCC) patients, evaluated some of the factors associated with it, and assessed its relationship with early detection of postoperative disease progression. METHODS: An exploratory retrospective cohort study of 430 OSCC patients was conducted. We examined associations of follow-up attendance within the first year after surgery with selected demographic and clinical factors, and with early detection of disease progression. RESULTS: The mean number of follow-up visits within the first year after surgery was 3.9 out of the 12 recommended at our center; few patients were fully adherent. Age ≥70 years, unmarried status, high education level, and negative history of surgery for premalignant or malignant lesions from oral cavity or other sites were significantly associated with lower follow-up attendance. Greater follow-up attendance was significantly associated with early detection of disease progression during the first year after surgery (p = 0.025). CONCLUSIONS: Adherence to follow-up visits was poor. Several sociodemographic and clinical factors were related to follow-up attendance, greater follow-up attendance was significantly associated with early detection of disease progression, and these should be further explored in future research.

pH-responsive dynamically cross-linked nanogels with effective endo-lysosomal escape for synergetic cancer therapy based on intracellular co-delivery of photosensitizers and proteins.

Co-delivery of photosensitizers (PSs) and protein drugs represents great potentiality for enhancing the efficiency of synergistic cancer therapy. However, the intricate tumor-microenvironment and the lack of nanoplatforms to co-deliver both into cancer cells and activate their functions significantly hinder the clinical translation of this combined approach for cancer treatment. Herein, a chlorine e6 (Ce6)-functionalized and pH-responsive dynamically cross-linked nanogel (Ce6@NG) is fabricated by formation of benzoic imine linkages between Ce6-modified methoxy poly (ethyleneglycol)-block-poly (diethylenetriamine)-L-glutamate-Ce6 [MPEG-b-P(Deta)LG-Ce6] and terephthalaldehyde as cross-linkers for effective intracellular co-delivery of Ce6 and cytochrome c (CC), which could form a novel combination therapy system (CC/Ce6@NGs). The pH-sensitive benzoic imine bonds in the CC/Ce6@NGs endow them with excellent systemic stability under normal physiological environment while this nanosystem can be further cationized to enhance cell uptake in acidic extracellular environment. Upon cellular internalization, CC/Ce6@NGs can rapidly escape from the endo/lysosomal compartments and subsequently activate Ce6 to generate cytotoxic singlet oxygen upon laser irradiation and release of CC to induce programmed cell death by complete cleavage of benzoic imines at more acidic intracellular environments. Importantly, the catalase-like activity of CC can decompose H2O2 to produce O2 for hypoxia alleviation and improvement of the photodynamic therapy (PDT) of cancer. Moreover, this enhanced synergistic anticancer activity is confirmed both in vitro and in vivo. In view of the versatile chemical conjugation, this research offers a promising and smart nanosystem for intracellular co-delivery of PSs and therapeutic proteins.

Factors affecting postoperative sleep quality of patients undergoing flap transfer for head and neck reconstruction.

OBJECTIVES: This study aimed to examine the postoperative sleep quality of patients undergoing flap transfer for head and neck reconstruction and to identify the associated factors. MATERIALS AND METHODS: We carried out a prospective cohort study of patients who underwent flap transfer for head and neck reconstruction at our institute between August 2020 and December 2021. The insomnia severity index (ISI) was used to examine the patients' sleep quality at postoperative week 1. Patients with an ISI score ≥ 15 were recognized as suffering from significant clinical insomnia. Descriptive statistics was used to expound the postoperative sleep quality. Associations between postoperative sleep quality and clinical variables were examined using the Chi-squared test and a Binary logistics regression model to identify the associated risk factors. RESULTS: Among the 101 patients included, their average ISI score was 15.6 (range 2-25), and 62 patients (61.4%) experienced significant clinical insomnia. Anxiety (odds ratio = 8.361; 95% confidence interval: 1.001-69.837; P = 0.049) and postoperative complications (odds ratio = 6.285; 95% confidence interval: 1.941-20.351; P = 0.002) were significantly associated with postoperative insomnia of the included patients. CONCLUSION: Postoperative sleep disturbances are highly prevalent among patients undergoing flap transfer for head and neck reconstruction, for which anxiety and postoperative complications are independent risk factors. Psychotherapy is necessary for patients with anxiety symptoms and measures should be taken to minimize the postoperative complications. Moreover, pain treatment is necessary to improve postoperative sleep quality and quality of life.

Familial left cervical neurofibromatosis 1 with scoliosis: A case report.

BACKGROUND: Neurofibromatosis type 1 (NF1) is an inherited autosomal dominant disorder affecting many parts of the body with café au lait spots, skeletal deformity, and scoliosis. A familial case of NF1 with scoliosis and a painless mass had not yet been reported. CASE SUMMARY: We describe the case of a 15-year-old male patient with a painless lump on the left side of his neck for 10 years and scoliosis. His right shoulder was about 5 cm lower than the left, the left side of his face was deformed, and the left submandibular skin was relaxed. The folding and drooping were obvious and movement was poor. Computed tomography revealed the involvement of the neck, upper chest wall, and surrounding left shoulder, accompanied by bone changes and scoliosis. Histological evaluation showed subepidermal pale blue mucoid degeneration, fibrous fusiform cells in the dermis in a fascicular, woven arrangement. His mother had the same medical history. The diagnosis was neurofibromatosis of the left neck. Various parts of the tumor tissue were serially resected during several visits. Eight months after surgery, there was a slight tendency to regrow. CONCLUSION: This case of slow-progressing NF1 highlights the importance of early diagnosis and treatment to reduce its impact on the patient's growth and development.

CD44-Targeted and Enzyme-Responsive Photo-Cross-Linked Nanogels with Enhanced Stability for In Vivo Protein Delivery.

One of the biggest challenges of the protein delivery system is to realize stable and high protein encapsulation efficiency in blood circulation and rapid release of protein in the targeted tumor cells. To overcome these hurdles, we fabricated enzyme-responsive photo-cross-linked nanogels (EPNGs) through UV-triggered chemical cross-linking of cinnamyloxy groups in the side chain of PEGylation hyaluronic acid (HA) for CD44-targeted transport of cytochrome c (CC). The EPNGs showed high loading efficiency and excellent stability in different biological media. Notably, CC leakage effectively suppressed under physiological conditions but accelerated release in the presence of hyaluronidase, an overexpressed enzyme in tumor cells. Moreover, thiazolylblue tetrazolium bromide (MTT) results indicated that the vacant EPNGs showed excellent nontoxicity, while CC-loaded EPNGs exhibited higher killing efficiency to CD44-positive A549 cells than to CD44-negative HepG2 cells and free CC. Confocal images confirmed that CC-loaded EPNGs could effectively be internalized by CD44-mediated endocytosis pathway and rapidly escape from the endo/lysosomal compartment. Human lung tumor-bearing mice imaging assays further revealed that CC-loaded EPNGs actively target tumor locations. Remarkably, CC-loaded EPNGs also exhibited enhanced antitumor activity with negligible systemic toxicity. These results implied that these EPNGs have appeared as stable and promising nanocarriers for tumor-targeting protein delivery.

Insights into the regulatory role of Plexin D1 signalling in cardiovascular development and diseases.

Plexin D1 (PLXND1), which was previously thought to mediate semaphorin signalling, belongs to the Plexin family of transmembrane proteins. PLXND1 cooperates mostly with the coreceptor neuropilin and participates in many aspects of axonal guidance. PLXND1 can also act as both a tumour promoter and a tumour suppressor. Emerging evidence suggests that mutations in PLXND1 or Semaphorin 3E, the canonical ligand of PLXND1, can lead to serious cardiovascular diseases, such as congenital heart defects, CHARGE syndrome and systemic sclerosis. Upon ligand binding, PLXND1 can act as a GTPase-activating protein (GAP) and modulate integrin-mediated cell adhesion, cytoskeletal dynamics and cell migration. These effects may play regulatory roles in the development of the cardiovascular system and disease. The cardiovascular effects of PLXND1 signalling have gradually been elucidated. PLXND1 was recently shown to detect physical forces and translate them into intracellular biochemical signals in the context of atherosclerosis. Therefore, the role of PLXND1 in cardiovascular development and diseases is gaining research interest because of its potential as a biomarker and therapeutic target. In this review, we describe the cardiac effects, vascular effects and possible molecular mechanisms of PLXND1 signalling.

A pH-activated charge convertible quantum dot as a novel nanocarrier for targeted protein delivery and real-time cancer cell imaging.

The rapid developments of nanocarriers based on quantum dots (QDs) have been confirmed to show substantial promise for drug delivery and bioimaging. However, optimal QDs-based nanocarriers still need to have their controlled behavior in vitro and in vivo and decrease heavy metal-associated cytotoxicity. Herein, a pH-activated charge convertible QD-based nanocarrier was fabricated by capping multifunctional polypeptide ligands (mPEG-block-poly(ethylenediamine-dihydrolipoic acid-2,3-dimethylmaleic anhydride)-L-glutamate, PEG-P(ED-DLA-DMA)LG) onto the surface of core/multishell CdSe@ZnS/ZnS QD by means of a ligand exchange strategy, followed by uploading of cytochrome C (CC) (CC-loaded QD-PEG-P(ED-DLA-DMA)LG) via electrostatic interactions, in which QDs that were water-soluble and protein-loading were perfectly integrated. That is, the CC-loaded QD-PEG-P(ED-DLA-DMA)LG inherited excellent fluorescence properties from CdSe@ZnS/ZnS QD for real-time imaging, as well as tumor-microenvironment sensitivities from PEG-P(ED-DLA-DMA)LG for enhanced cellular uptake and CC release. Experimental results verified that the QD-PEG-P(ED-DLA-DMA)LG showed enhanced internalization, rapid endo/lysosomal escape, and supplied legible real-time imaging for lung carcinoma cells. Furthermore, pH-triggered charge-convertible ability enabled the QD-PEG-P(ED-DLA-DMA)LG-CC to effectively kill cancer cells better than did the control groups. Hence, constructing smart nanocomposites by facile ligand-exchange strategy is beneficial to QD-based nanocarrier for tumor-targeting cancer therapy.

Advances in biodegradable and injectable hydrogels for biomedical applications.

In situ-forming injectable hydrogels are smart biomaterials that can be implanted into living bodies with minimal invasion. Due to pioneer work of Prof. Sung Wan Kim in this field, injectable hydrogels have shown great potentials in many different biomedical applications. Biodegradable and injectable hydrogels can be administered at room temperature as viscous polymer sols. They will degrade after accomplishing their tasks. Before injecting into living bodies, active substances can be loaded into viscous polymer sols with a high loading efficiency by simple mixing. After injecting into living bodies, active substances-loaded hydrogels can be formed and active substances can be released in a controlled manner upon diffusion or polymer degradation. Due to their outstanding properties and unique features, injectable hydrogels are very promising in many biomedical applications including drug/protein/gene delivery, tissue engineering, and regenerative medicine. In this review, we briefly introduce recent development of several important types of in situ-forming injectable hydrogels reported by our group during the last three years. Important properties and potential applications (such as cancer therapy, insulin release and wound healing) of these injectable hydrogels are reviewed. Challenges and perspectives in this research field are also discussed.

Intracellular delivery of cytochrome C using hypoxia-responsive polypeptide micelles for efficient cancer therapy.

To begin with, it is important to note that biodegradable polypeptides have been extensively applied as drug delivery carriers due to their excellent bioavailability, neglectful toxicity, good encapsulation and controlled release. Thus, a biodegradable and hypoxia-responsive polypeptide is a benefit when synthesized for the intracellular delivery of cytochrome c (CC). In its most positive context, this amphiphilic polypeptide can self-assemble into core/shell-structured micelles and encapsulate CC in their hydrophobic cores. Owing to the presence of hypoxia-responsive chemical bonds, the CC-loaded polymeric micelles (PMs) can potentially target hypoxic tissues (such as tumors) and release the proteins inside the cancer cells. For this reason, these PMs exhibit high protein loading content and efficiency and remain stable in several different kinds of cell culture media under normoxic condition. Moreover, the confocal microscopy indicates that CC-loaded PMs could be effectively uptaken by cancer cells and accelerate endo/lysosomal escape. Most importantly, the CC-loaded PMs show great killing effect to HepG2 liver cancer cells under hypoxic condition, which makes this nano-platform a promising candidate for use with efficient cancer therapy.

Dual activatable self-assembled nanotheranostics for bioimaging and photodynamic therapy.

Multifunctional nanosystems that can transport therapeutic and diagnostic agents into tumor sites and activate their respective functions via tumor-microenvironment recognition are highly desirable for clinical applications. We fabricated pH and redox dual-activatable self-assembled nanotheranostics (named as DA-SNs) via coordination-driven self-assembly of chlorin e6 (Ce6) disulfide-linked pH sensitive polymer ligand, poly (isobutylene-alt-maleic anhydride-graft-methoxy-poly (ethyleneglycol)-graft-imidazole-graft-Cystamine-Ce6) [PIMA-mPEG-API-SS-Ce6], and gadolinium ions (Gd3+). DA-SNs exhibited uniform particle size of ~48 nm, excellent stability, and inherent biosafety. Negatively charged DA-SNs could prolong blood circulation time (t1/2 = 2.91 h) and improve tumor accumulation. Moreover, DA-SNs could undergo surface charge switch from negative charge to positive one in a slightly acidic tumor extracellular environment (pH 6.8), thus enhancing cellular uptake. After entering tumor cells, fluorescence, photodynamic therapeutic activity, and T1MR contrast from DA-SNs could be activated within this intracellular environment with lowered pH and high level of GSH. Importantly, human tumors implanted in mice could be successfully visualized via distinct pH and redox dual-sensitive T1MR contrast and fluorescence imaging, indicating that DA-SNs could serve as a dual-modal MR/fluorescence imaging probe for tumor-targeting diagnosis. In addition, DA-SNs exhibited superior photodynamic therapeutic efficiency with negligible side effects. Therefore, this DA-SN shows great promise for synergistic photodynamic therapy and diagnostic imaging.

Mucoepidermoid carcinoma in the infratemporal fossa: A case report.

BACKGROUND: Mucoepidermoid carcinoma is the most common primary epithelial salivary gland malignancy. It mostly occurs in the major or intraoral minor salivary glands but rarely in the infratemporal fossa. Here, we present a case of aggressive mucoepidermoid carcinoma in the infratemporal fossa with neck lymph node metastasis and also discuss diagnostic and treatment strategies. CASE SUMMARY: A 39-year-old woman with a mass located in the right submandibular area presented to our department. Physical examination revealed lymphadenopathy on the right submandibular side measuring 2.5 cm × 3 cm that was hard and had poor mobility. Results of nasal endoscopy were unremarkable. Ultrasound examination revealed an enlarged lymph node at level II of the right side. Fine needle aspiration cytology of the metastatic lymph node revealed malignant cells with infection. Contrast-enhanced computed tomography revealed an enhancing ill-defined soft tissue mass in the right infratemporal region. Positron emission tomography/computed tomography revealed hyperintensity in the right infratemporal fossa along with lymphadenopathy at level II of the right-side lymph node. The patient underwent extended resection of the primary tumor, and ipsilateral radical neck dissection was also completed. Hematoxylin-eosin staining and immunohistochemistry revealed a high-grade mucoepidermoid carcinoma. No signs and symptoms of recurrence of the neoplasm were present after 20 mo of follow-up. CONCLUSION: Positron emission tomography/computed tomography play a key role in primary tumor localization. Furthermore, histopathology and immunohistochemistry play pivotal roles in disease diagnosis.