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Localized photodynamic therapy (PDT) uses a polymeric-photosensitizer (PS)-embedded, covered self-expandable metallic stent (SEMS). PDT is minimally invasive and a noteworthy potential alternative for treating esophageal strictures, where surgery is not a viable option. However, preclinical evidence is insufficient, and optimized irradiation energy dose ranges for localized PDT are unclear. Herein, we validated the irradiation energy doses of the SEMS (embedded in a PS using chlorin e6 [Ce6] and covered in silicone) and PDT-induced tissue changes in a rat esophagus. Cytotoxicity and phototoxicity in the Ce6-embedded SEMS piece with laser irradiation were significantly higher than that of the silicone-covered SEMS with or without laser and the Ce6-embedded silicone-covered SEMS without laser groups (all p< 0.001). Moreover, surface morphology, atomic changes, and homogeneous coverage of the Ce6-embedded silicone-covered membrane were confirmed. The ablation range of the porcine liver was proportionally increased with the irradiation dose (all p< 0.001). The ablation region was identified at different irradiation energy doses of 50, 100, 200, and 400 J/cm2. The in vivostudy in the rat esophagus comprised a control group and 100, 200, and 400 J/cm2energy-dose groups. Finally, histology and immunohistochemistry (TUNEL and Ki67) confirmed that the optimized Ce6-embedded silicone-covered SEMS with selected irradiation energy doses (200 and 400 J/cm2) effectively damaged the esophageal tissue without ductal perforation. The polymeric PS-embedded silicone-covered SEMS can be easily placed via a minimally invasive approach and represents a promising new approach for the palliative treatment of malignant esophageal strictures.

Purpose: Psoriasis, a globally prevalent chronic skin condition affecting 2–5% of the world’s population, significantly deteriorates patients’ quality of life. Psoriasis is an immune-mediated skin disorder triggered by abnormal activation of keratinocytes in the epidermis, leading to excessive skin cell turnover. Local therapies serve as the cornerstone of psoriasis treatment, ranging from mild to severe cases. Despite efforts in drug development, patient satisfaction remains limited. Most psoriasis treatments encounter challenges in local delivery due to their low solubility and stability. Methods: To overcome these challenges, we developed a thymoquinone (TQ)-loaded oil-in-water layered double hydroxide (LDH) nanosheet Pickering emulsion (TLE) using exfoliated LDH nanosheets (LDH NSs), oleyl alcohol, and TQ. TQ, a naturally derived anti-inflammatory agent, was employed for the treatment of psoriasis. LDH NSs were used as emulsifiers for oleyl alcohol instead of traditional surfactants to produce Pickering-style emulsions. Results: In in vitro cadaver skin penetration experiments, the Pickering structure LDH emulsion (LE) accumulated in the stratum corneum and subsequently released the drug into the dermal layer. Additionally, owing to the inherent UV-shielding properties of LDH, TLE exhibited enhanced photostability when TQ was encapsulated within LDH oil droplets. Compared with the TQ-loaded polysorbate emulsion, TLE demonstrated 20.5% greater TQ absorption after solar irradiation, indicating the superior photostability of LE. Upon the application of TLE in an imiquimod-induced psoriatic mouse model, significant therapeutic effects were observed without any adverse side effects. Conclusion: This study demonstrated the excellent efficacy of LE derived from enhanced skin penetration, suggesting its potential as a transdermal drug delivery platform for various conditions.

Purpose:To investigate the clinical effects of head-mounted display on the refractive error and oculomotor system in normal adolescents.Methods:Sixty volunteers (age: 13 to 18 years) watched a three-dimensional movie and virtual reality application of head-mounted display for 30 minutes. The refractive error (diopters [D]), angle of deviation (prism diopters [PD]) at distance (6 m) and near (33 cm), near point of accommodation, and stereoacuity were measured before, immediately after, and 10 minutes after watching the head-mounted display. The refractive error was presented as spherical equivalent (SE). Refractive error was measured repeatedly after every 10 minutes when a myopic shift greater than 0.15 D was observed after watching the head-mounted display.Results:The mean age of the participants was 14.7 ± 1.3 years and the mean SE before watching head-mounted display was −3.1 ± 2.6 D. One participant in the virtual reality application group was excluded due to motion sickness and nausea. After 30 minutes of watching the head-mounted display, the SE, near point of accommodation, and stereoacuity in both eyes did not change significantly (all The mean age of the participants was 14.7 ± 1.3 years and the mean SE before watching head-mounted display was −3.1 ± 2.6 D. One participant in the virtual reality application group was excluded due to motion sickness and nausea. After 30 minutes of watching the head-mounted display, the SE, near point of accommodation, and stereoacuity in both eyes did not change significantly (all P> .05). Immediately after watching the head-mounted display, esophoric shift was observed (0.6 ± 1.5 to 0.2 ± 1.5 PD), although it was not significant (P= .06). Transient myopic shifts of 17.2% to 30% were observed immediately after watching the head-mounted display in both groups, but recovered fully within 40 minutes after watching the head-mounted display.Conclusions:There were no significant clinical effects of watching head-mounted display for 30 minutes on the normal adolescent eye. Transient changes in refractive error and binocular alignment were noted, but were not significant.[[J Pediatr Ophthalmol Strabismus. 2016;53(4):238–245.]

Herein, we present human adipose-derived stem cells (ADSCs) inserted with the receptor-interacting protein kinase-3 (RIP3) gene (RP@ADSCs), which induces cell necroptosis, for tumor immunotherapy. Necroptosis has characteristics of both apoptosis, such as programmed cell death, and necrosis, such as swelling and plasma membrane rupture, during which damage-related molecular patterns are released, triggering an immune response. Therefore, necroptosis has the potential to be used as an effective anticancer immunotherapy. RP@ADSCs were programmed to necroptosis after a particular time after being injected in vivo, and various pro-inflammatory cytokines secreted during the stem cell death process stimulated the immune system, showing local and sustained anticancer effects. It was confirmed that RIP3 protein expression increased in ADSCs after RP transfection. RP@ADSCs continued to induce ADSCs death for 7 days, and various pro-inflammatory cytokines were secreted through ADSCs death. The efficacy of RP@ADSCs-mediated immunotherapy was evaluated in mouse models bearing GL-26 (glioblastoma) and K1735 (melanoma), and it was found that RP resulted in an increase in the population of long-term cytotoxic T cells and a decrease in the population of regulatory T cells. This shows that RP@ADSCs have potential and applicability as an excellent anticancer immunotherapy agent in clinical practice.

Recently, stem cells and their secretomes have attracted great attention in biomedical applications, particularly extracellular vesicles (EVs). EVs are secretomes of cells for cell-to-cell communication. They play a role as intercellular messengers as they carry proteins, nucleic acids, lipids, and therapeutic agents. They have also been utilized as drug-delivery vehicles due to their biocompatibility, low immunogenicity, stability, targetability, and engineerable properties. The therapeutic potential of EVs can be further enhanced by surface engineering and modification using functional molecules such as aptamers, peptides, and antibodies. As a consequence, EVs hold great promise as effective delivery vehicles for enhancing treatment efficacy while avoiding side effects. Among various cell types that secrete EVs, stem cells are ideal sources of EVs because stem cells have unique properties such as self-renewal and regenerative potential for transplantation into damaged tissues that can facilitate their regeneration. However, challenges such as immune rejection and ethical considerations remain significant hurdles. Stem cell-derived EVs have been extensively explored as a cell-free approach that bypasses many challenges associated with cell-based therapy in cancer therapy and tissue regeneration. In this review, we summarize and discuss the current knowledge of various types of stem cells as a source of EVs, their engineering, and applications of EVs, focusing on cancer therapy and tissue engineering.

Herein, we introduce a novel approach involving the utilization of a human serum albumin-coated zeolite imidazolate framework-8 containing a photosensitizer (HPZ) that exhibits targeted recognition of the tumor microenvironment, enabling the rapid elevation of zinc ion concentrations while facilitating the controlled release of an encapsulated photosensitizer (PS). At a physiological pH of 7.4, HPZ demonstrates a size of approximately 170 nm, significantly decreasing to less than 10 nm under pH 6.5 acidic conditions. Acid-induced decomposition of HPZ triggers a rapid increase in zinc ion concentration, eliciting potent cytotoxic effects against colorectal, breast, and pancreatic cancers. Additionally, upon laser irradiation, the encapsulated PS within HPZ initiates the generation of reactive oxygen species, synergistically augmenting the cytotoxicity induced by zinc ions. Intravenous administration of HPZ in a CT26 tumor-bearing mouse model resulted in a notable expansion of CD3+CD4+helper T cells and CD3+CD8+cytotoxic T cells, accompanied by a reduction in the CD4+CD25+Foxp3+regulatory T-cell population. These changes led to significant inhibition of tumor growth, highlighting the efficacy of HPZ in this experimental model. Importantly, HPZ exhibits favorable safety characteristics, displaying no toxicity toward vital organs and inducing no weight loss. Thus, HPZ holds immense promise as a standalone treatment or in combination with diverse anticancer immunotherapies, underscoring its potential in the field of anticancer immunotherapy.

Here, we describe an intracellular pH-regulating nanoparticle (IPRN), coencapsulated with chemosensitizers and anticancer agents for effective and safe cancer treatment. IPRN contains a tubulysin derivative (TUB), a hydrophobic anticancer drug, and pantoprazole (PTZ), a hydrophilic proton-pump inhibitor. IPRN with a size of 62 nm has an anionic surface charge and is stable for at least two weeks under storage conditions, though PTZ and TUB encapsulated in IPRN showed different drug release patterns. PTZ was released before TUB, controlling the cancer’s intracellular pH, maintaining a pH at which TUB can work well. The encapsulated PTZ increased the pH of endolysosomes and inhibited ion trapping, with TUB ionization, thereby exhibiting increased cytotoxicity compared with free TUB observed in various cancer cell lines, such as human liver adenocarcinoma, human glioblastoma, and human pancreatic carcinoma. IPRN exhibited a 1.9-fold improved tumor growth inhibitory effect in a human liver adenocarcinoma-bearing mouse model, while minimizing the hepatotoxicity of free TUB. Thus, nanomedicines that contain both a chemosensitizer and an anticancer agent, such as IPRN, are expected to be next-generation anticancer agents that reduce the side effects of anticancer drugs and increase the therapeutic effect.

Purpose: In the present study, we describe an aronia extract (AE) and carrageenan (CGN) nanocomplex (ACNC) for intranasal administration that directly blocks and prevents viral infection in the respiratory tract. Methods: To evaluate the characteristics of the ACNC, size measurements were performed by dynamic light scattering (DLS) and scanning electron microscope (SEM). Viscosity and pH evaluations at 4, 25, and 37 °C were performed. DPPH assays were performed to evaluate the antioxidant activity of the ACNC. The antiviral efficacy of the ACNC was evaluated using viral plaque reduction assays in vitro. The inhibition of influenza A virus infection was evaluated by intranasal administration of the ACNC. Results: The ACNC was manufactured by electrostatic interactions, and it maintained a stable state in 4, 25, and 37 °C. The viscosity of the ACNC increased with carrageenan concentration and temperature. The ACNC had a viscosity that allowed binding to nasal mucus and had a spray angle greater than 19°, resulting in an appropriate complex to be applied for nasal administration. The ACNC maintained the antioxidant and antiviral effects of AE and CGN, respectively. In particular, the ACNC exhibited 4.8-fold and 2.4-fold lower IC50and IC90concentrations than AE and CGN alone, respectively. The ACNC prevented influenza A virus infection by intranasal administration to the nasal cavity with 100% efficiency without weight loss. Conclusion: Because the antiviral effect of this type of nanocomposite is not affected by the modification of the viral structure, it is a potential method for the prevention of various viral infections.

Bariatric surgery is the most effective treatment for weight recidivism, and endoscopic bariatric treatment has been developed for a similar effect without anatomical modification. An intragastric satiety-inducing device (ISD) is a minimally invasive approach to induce satiety by continuously pressing the stomach and stimulating ghrelin-producing cells. To enhance the therapeutic effects of ISD, photodynamic therapy (PDT) can be combined by generating singlet oxygen under laser irradiation. Methylene blue (MB), as a photosensitizer (PS), was coated on the ISD surface for singlet oxygen production to stimulate or destroy cells. Ghrelin-producing cells effectively inhibited ghrelin secretion and induced gastrointestinal satiety signals compared with the MB-uncoated device via PDT. Herein, MB-embedded ISDs were developed, and their photoresponsive abilities were demonstrated in the device itself and in vitro. PDT with an MB-embedded ISD was successfully performed in a porcine model, which had 2-fold reduced body weight gain (12% in PDT vs 24% in control) and 2-fold reduced ghrelin levels (21.2 pg/mL in PDT vs 45.1 pg/mL in control) at the first week postprocedure. The simple and unique operation extends the point of view in PDT and is expected to be a novel endoscopic bariatric therapy.

To supplement shortcomings of existing treatments and enhance the therapeutic effect for liver cancer, a novel photosensitizer is designed using silicon phthalocyanine (SiPC) and a unique targeting moiety, glycyrrhetinic acid (GA). The SiPC is modified with a hydrophilic polymer and finally bound with GA. The solubility, fluorescence, singlet oxygen generation, and UV–vis absorbance are analyzed, and receptor-dependent intracellular influx is estimated in various cell lines. Using flow cytometry and confocal microscopy, intracellular fluorescence was detected in liver cancer because of GA receptor overexpression. To prove in vitrophotodynamic therapeutic effects, the sample treated cells are irradiated and viability of liver cancer cells decreases in proportion to laser power. Then, it is confirmed that GA-modified SiPC effectively accumulated in liver cancer of HepG2 tumor-bearing mouse. Additionally, the PDT-combined therapeutic effect of GA-modified SiPC is observed in the tumor model and shown to have a tumor growth inhibition effect (60.36 times higher than the control group) and supported by histological analyses. These results demonstrate that the newly modified SiPC can be applied to liver cancer-specific treatment with high therapeutic efficacy. Consequently, novel SiPC has the potential to alter conventional liver cancer-targeted therapy and chemotherapy in clinical use.

Carbonized iodine-doped particles (CIPs) were developed to overcome the disadvantages of computed tomography (CT) contrast agents, such as high osmolality and the radiodensity dilution of monomolecular contrast agents and low solubility and high toxicity of polymeric contrast agents. The CIPs were synthesized via a hydrothermal synthesis for 8 h using ATIPA (5-amino-2,4,6-triiodoisophthalic acid), glycerol, and tromethamine in the presence of D.W. (deionized water)-insoluble ATIPA converted into CIPs through a hydrothermal synthesis, showing high solubility and low osmotic pressure. The in vitrocontrast effect determined for the resulting CIPs demonstrated a 57.6% enhancement compared to iohexol, and the osmotic pressure of the resulting CIPs was lower than that of iohexol. In addition, the CIPs demonstrated no dilution-induced contrast decrease in plasma and, therefore, demonstrated high contrast strength in vivo. Cytotoxicity tests, hemolysis assays, and histological analyses were conducted to verify the biocompatibility of the CIP product; however, no toxicity was observed. Furthermore, the CIP demonstrated a much higher contrast effect than iohexol at low concentrations. These results indicate that the CIP we have produced may be used as an effective blood pool agent for CT imaging.

Multifunctional drug delivery systems were designed and engineered by template synthesis of a microporous organic polymer (MOP) and by postsynthetic modification. Hollow MOP spheres bearing Fe3O4yolks (Fe3O4@Void@MOP) were prepared by the synthesis of MOP on Fe3O4@SiO2nanoparticles and by successive silica etching. In addition to the magneto-thermal function of Fe3O4yolks, an aggregation-induced emission (AIE) feature was incorporated into the Fe3O4@Void@MOP through a homocoupling of tetra(4-ethynylphenyl)ethylene to form Fe3O4@Void@MOP-TE. Folate groups were further introduced into Fe3O4@Void@MOP-TE through the postsynthetic modification based on the thiol-yne click reaction. The resultant Fe3O4@Void@MOP-TE-FA showed multifunctionality in antitumoral therapy viafolate receptor targeting, doxorubicin delivery, AIE-based imaging, and the magneto-thermal feature.

Recent cancer immunotherapy has attracted much attention due to high specificity and recurrence prevention of tumor. Nevertheless, its therapeutic effects are still challenging in solid cancer. To establish superior antitumor immunity, chlorin e6 (Ce6)-loaded pH sensitive carbon dots were investigated (Ce6@IDCDs). At tumoral pH 6.5, Ce6 was released four times compared with the release at physiological pH 7.4 due to an imbalance between hydrophilic and hydrophobic forces via protonation of imidazole groups in Ce6@IDCDs. This result led to the superior singlet oxygen generating activity of Ce6@IDCDs without Ce6 quenching. The maturation effects of dendritic cells after co-incubation with supernatant media obtained from Ce6@IDCDs with laser-treated cells at pH 6.5 were much higher than at physiological pH. Furthermore, Ce6@IDCDs following a laser at pH 6.5 significantly promoted calreticulin exposure and high-mobility group box 1 release, as major immunogenic cell death markers. In bilateral CT-26-bearing mice model, the Ce6@IDCDs elicited significant antitumoral effects at laser treated-primary tumor regions via therapeutic reactive oxygen species. Furthermore, Ce6@IDCDs upon laser irradiation induced a large amount of activated CD8+T cells, natural killer cells, and mature dendritic cells recruitment into tumoral tissue and hampered tumor growth even at untreated sites approximately four-fold compared with those of others. Overall, this pH-sensitive immunoinducer can accomplish primary and distant tumor ablation via photomediated cancer immunotherapy.

A cancer vaccine is a promising immunotherapy modality, but the heterogenicity of tumors and substantial time and costs required in tumor-associated antigen (TAA) screening have hindered the development of an individualized vaccine. Herein, we propose in situvaccination using cancer-targetable pH-sensitive zinc-based immunomodulators (CZIs) to elicit antitumor immune response against TAAs of patients’ tumors without the ex vivoidentification processes. In the tumor microenvironment, CZIs promote the release of large amounts of TAAs and exposure of calreticulin on the cell surface via immunogenic cell death through the combined effect of excess zinc ions and photodynamic therapy (PDT). With these properties, CZIs potentiate antitumor immunity and inhibit tumor growth as well as lung metastasis in CT26 tumor-bearing mice. This nanoplatform may suggest an alternative therapeutic strategy to overcoming the limitations of existing cancer vaccines and may broaden the application of nanoparticles for cancer immunotherapy.

Purpose: To evaluate the efficacy of Faden procedure for correcting consecutive esotropia (ET). Methods: This retrospective study included 25 children who developed consecutive ET after primary bilateral lateral rectus (BLR) recession and underwent medial rectus (MR) recession with the Faden procedure (Faden group) or MR recession only (control group) between 2013 and 2018. Postoperative deviation angles were evaluated at each follow-ups until postoperative 6-month visit. Surgical motor and sensory outcomes were compared between Faden group and control group. Results: There were 10 children in the Faden group and 15 children in the control group. While the Faden group maintained orthotropia without any small deviation until postoperative 6-month visit, the control group showed wider distribution of postoperative deviation angles (1 patient with small angle esodeviation &lt; 5 PD, 3 patients with esodeviation > 5 PD, and 3 patients with exodeviation &lt; 5 PD). In the Faden group, seven patients have good stereopsis (60″ or better) and three patients demonstrated fair stereopsis (80–3000″) after surgery. In the control group, four, eight, and three patients showed good, fair, and nil stereopsis (P= 0.026), respectively. Conclusion: MR recession combined with Faden operation could be a good surgical option for managing consecutive ET.

Although memory functions of immune cells characterized by increased resistance to subsequent infections after initial pathogen exposure are well-established, it remains unclear whether non-immune cells, especially tissue-resident stem cells, exhibit similar memory mechanisms. The present study revealed that detrimental effects of initial viral antigen exposure (human papillomavirus, HPV) on diverse stem cell functions were significantly exacerbated upon subsequent secondary exposure both in vitroand in vivo. Importantly, endometrial stem cells exhibited robust memory functions following consecutive HPV antigen exposures, whereas fully differentiated cells such as fibroblasts and vesicular cells did not show corresponding changes in response to the same antigen exposures. Deficiency of angiopoietin-like 4 (ANGPTL4) achieved through shRNA knockdown in vitroand knockout (KO) mice in vivohighlighted the critical role of ANGPTL4 in governing memory functions associated with various stem cell processes. This regulation occurred through histone H3 methylation alterations and PI3K/Akt signaling pathways in response to successive HPV antigen exposures. Furthermore, memory functions associated with various stem cell functions that were evident in wild-type (WT) mice following consecutive exposures to HPV antigen were not observed in ANGPTL4 K.O mice. In summary, our findings strongly support the presence of memory mechanism in non-immune cells, particularly tissue-resident stem cells.

Nonpolymer, pH-sensitive carbon dots (pSCDs) were developed to overcome the disadvantages of pH-sensitive polymers such as inevitable synthesis, wide distribution of molecular weight, uncontrolled loading and release rate of drugs, and toxicity by biodegradation. The pSCDs were synthesized via one spot synthesis for 3 min using citric acid (CA) and 1-(3-aminopropyl) imidazole (API). Imidazole groups were present on pSCD surfaces and facilitated DOX loading via hydrophobic interactions (loading efficiency: 78.55%). The DOX-loaded pSCDs collapsed at tumoral pH (pH ∼ 6.5) due to protonation of the imidazole groups, and DOX was released about 7 times higher than the control group. The therapeutic effect was confirmed in vitro using HCT-116 (human colon cancer), PANC-1 (human pancreatic cancer), and SKBR-3 (human breast cancer) cells. Additionally, the DOX-loaded pSCDs successfully inhibited tumor growth in an HCT-116-bearing mouse model and did not show toxicity. These results indicate that a nonpolymeric pSCDs platform has the potential to be used as a cancer targeting therapeutic material.

A combination of chemo-photodynamic therapy has been manifested as a promising strategy for efficient cancer treatment due to the enhanced therapeutic efficacy. Here, we designed doxorubicin (DOX)-loaded photoresponsive micelles (DPRMs) based on a combination of chlorin e6 (Ce6) and lipoic acid (LA) conjugated methoxy-poly(ethylene) glycol (mPEG-Ce6, mPEG-LA) to achieve effective drug delivery using a single system. DPRMs were optimized with different molar ratios of mPEG-Ce6 and mPEG-LA which showed uniformly spherical morphology of size ∼130 nm and approximately 9% of DOX loading contents. Photoresponsive lipoyl ring of mPEG-LA was incorporated in DPRMs in order to induce photomediated reduction resulting in 2–3-fold accelerated DOX release according to higher molar ratio of mPEG-LA and enhancement of light dose. The photoresponsive DOX release and ROS generation by Ce6 mediated cytotoxic effect of DPRMs were demonstrated in vitro using CT-26 (mouse colon cancer) and HCT-116 (human colon cancer) cells. We observed both the photosensitizer and the anticancer drug are colocalized in the tumor cells to achieve effective enhancement. Additionally, the DPRMs with laser irradiation successfully inhibited tumor growth in CT-26 tumor bearing mouse model and immunohistochemical staining verified apoptosis-mediated tumor growth inhibition. These observations demonstrated that the DPRMs showed a higher therapeutic effect than the other systems and PDT maximized the antitumor effect. Thus, DPRMs confirmed the advantages as a chemo-photodynamic dual-therapy with a synergistic therapeutic effect and great potential for cancer treatment.

Here, a novel approach is presented to improve the efficacy of antibody‐drug conjugates (ADC) by integrating antibody‐mediated immunotherapy and photodynamic therapy (PDT) in a combination therapy system utilizing an antibody‐photosensitizer conjugate (APC) platform based on a poloxamer polymer linker. To specifically target Kirsten rat sarcoma 2 viral oncogene homolog (KRAS)‐mutated cancer cells, an antibody antiepidermal growth factor receptor (EGFR), cetuximab, with a poloxamer linker coupled with the photosensitizer chlorin e6 through click chemistry (cetuximab‐maleimide‐poly(ethylene oxide)‐poly(propylene oxide)‐poly(ethylene oxide)‐chlorine e6 conjugate, CMPXC) is synthesized. CMPXC is cytotoxic upon laser treatment, achieving a 90% cell death by suppressing KRAS downstream signaling pathways associated with ERK and AKT proteins, confirmed using RNA sequencing analysis. In KRAS‐mutated colorectal cancer mouse models, CMPXC significantly enhances antitumor efficacy compared with cetuximab treatment alone, resulting in an 86% reduction in tumor growth. Furthermore, CMPXC treatment leads to a 2.24‐ and 1.75‐fold increase in dendritic and priming cytotoxic T cells, respectively, highlighting the immune‐activating potential of this approach. The findings suggest that the APC platform addresses the challenges associated with ADC development and EGFR‐targeted therapy, including the synergistic advantages of antibody‐mediated immunotherapy and PDT. To improve the efficacy of antibody‐drug conjugates, a novel platform by combining antibody‐mediated immunotherpay and photodynamic therapy is constructed. Upon spatiotemporal light exposure, the antibody‐photosensitizer conjugate exhibits a remarkable anticancer effect, independent Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutation, by suppressing KRAS downstream signaling pathways and providing innate and adaptive immune system induction through a synergistic approach.

Purpose:To investigate the development pattern and related factors of postoperative re-drift in infantile esotropia.Methods:A total of 112 patients with infantile esotropia who underwent surgery before 3 years of age were included. Surgical outcomes were divided into (1) consecutive exotropia: more than 8 prism diopters (PD) of exodeviation; (2) recurrent esotropia: more than 8 PD of esodeviation; and (3) monofixation syndrome: maintenance of deviations within 8 PD. The occurrence rate, time of onset, and associated factors of the re-drift were evaluated.Results:At a mean follow-up of 9.5 years, consecutive exotropia developed in 37 patients (33.0%) and recurrent esotropia in 43 patients (38.4%). Whereas 76.7% of total recurrent esotropia cases were identified within postoperative 1 year, consecutive exotropia occurred constantly over 10 years postoperatively. The mean time to consecutive exotropia development from surgery was 78.6 months, greater than that of recurrent esotropia development (8.9 months) (At a mean follow-up of 9.5 years, consecutive exotropia developed in 37 patients (33.0%) and recurrent esotropia in 43 patients (38.4%). Whereas 76.7% of total recurrent esotropia cases were identified within postoperative 1 year, consecutive exotropia occurred constantly over 10 years postoperatively. The mean time to consecutive exotropia development from surgery was 78.6 months, greater than that of recurrent esotropia development (8.9 months) (P< 0.001). In multinomial logistic regression using monofixation syndrome as the reference category, fixation preference before surgery (odds ratio [OR]: 6.64, 95% confidence interval [CI]: 2.07 to 21.32) and the rate of myopic progression (OR: 15.07 per −1.00 D/year, 95% CI: 1.23 to 184.86) were associated with consecutive exotropia, whereas increase in the angle of esodeviation on postoperative day 1 (OR: 1.15, 95% CI: 1.04 to 1.26) was correlated with recurrent esotropia.Conclusions:This study demonstrates a difference between the development pattern of exotropic and esotropic drift after infantile esotropia surgery. Detailed preoperative assessment and close postoperative observation of deviations and refractive status will help to determine surgical outcomes of infantile esotropia.[[J Pediatr Ophthalmol Strabismus. 2018;55(2):128–134.]

Photodynamic therapy (PDT) is performed using a photosensitizer and light of specific wavelength in the presence of oxygen to generate singlet oxygen and reactive oxygen species(ROS) in the cancer cells. The accumulated photosensitizers in target sites induce ROS generation upon light activation, then the generated cytotoxic reactive oxygen species lead to tumor cell death via apoptosis or necrosis, and damages the target sites which results tumor destruction. As a consequence, the PDT-mediated cell death is associated with anti-tumor immune response. In this paper, the effects of PDT and immune response on tumors are reviewed. Activation of an immune response regarding the innate and adaptive immune response, interaction with immune cells and tumor cells that associated with antitumor efficacy of PDT are also discussed.

Photodynamic therapy (PDT) based upon the use of light and photosensitizers (PSs) has been used as a novel treatment approach for a variety of tumors. It, however, has several major limitations in the clinic: poor water solubility, long-term phototoxicity, low tumor targeting efficacy, and limited light penetration. With advances in nanotechnology, materials science, and clinical interventional imaging procedures, various smart-PSs have been developed for improving their cancer-therapeutic efficacy while reducing the adverse effects. Here, we briefly review state-of-the-art smart-PSs and discuss the future directions of PDT technology.

Bare metal stents (BMSs) have been studied in the treatment of tubular organ occlusion, but restenosis remains a problem with this type of therapy. Drug eluting stents (DESs) were developed afterwards to treat and prevent re-stenosis. Clinical studied have proven the efficacy of DESs for the prevention of smooth muscle and cancer cell proliferations. Coating DESs with a polymer facilitates sustained drug release by diffusion, degradation, and osmosis. To control drug delivery in DESs, the drug and polymeric materials-including their physicochemical properties-must be taken into consideration. It is important to understand polymeric materials for the development drug delivery technologies. This review highlights the studies on drug delivery system based on polymeric material used in DESs and the role of polymeric materials in DESs for drug delivery.

Transcatheter hepatic intra-arterial (IA) injection has been considered as an effective targeted delivery technique for hepatocellular carcinoma (HCC). Recently, drug-eluting beads (DEB) were developed for transcatheter IA delivery to HCC. However, the conventional DEB has offered relatively modest survival benefits. It can be difficult to control drug loading/release from DEB and to monitor selective delivery to the targeted tumors. Embolized DEBs in hepatic arteries frequently induce hypoxic and low pH conditions, promoting cancer cell growth. In this study, an acidic pH-triggered drug-eluting nanocomposite (pH-DEN) including superparamagnetic iron oxide nanocubes and pH-responsive synthetic peptides with lipid tails [octadecylamine–p(API-l-Asp)10] was developed for magnetic resonance imaging (MRI)-monitored transcatheter delivery of sorafenib (the only FDA-approved systemic therapy for liver cancer) to HCC. The synthesized sorafenib-loaded pH-DENs exhibited distinct pH-triggered drug release behavior at acidic pH levels and highly sensitive MR contrast effects. In an orthotopic HCC rat model, successful hepatic IA delivery and distribution of sorafenib-loaded pH-DEN was confirmed with MRI. IA-delivered sorafenib-loaded pH-DENs elicited significant tumor growth inhibition in a rodent HCC model. These results indicate that the sorafenib–pH-DENs platform has the potential to be used as an advanced tool for liver-directed IA treatment of unresectable HCC.

Achieving effective mRNA expression in vivorequires careful selection of an appropriate delivery vehicle and route of administration. Among the various routes of administration, intranasal administration has received considerable attention due to its ability to induce potent immune responses. In this context, we designed a specialized cationic polymer tailored for delivery of mRNA into the nasal cavity. These polymers are designed with varying degrees of substitution in different amine groups to allow for identification of the most suitable amine moiety for effective mRNA delivery. We also incorporated a photosensitizer within the polymer structure that can trigger the generation of reactive oxygen species when exposed to light. The synthesized cationic polymer is complexed with anionic mRNA to form a polyplex. Illuminating these polyplexes with laser light enhances their escape from intracellular endosomes, stimulating mRNA translocation into the cytoplasm, followed by increased mRNA expression at the cellular level. Through intranasal administration to C57BL/6 mice, it was confirmed that these photoactive polyplexes effectively induce mRNA expression and activate immune responses in vivousing photochemical effects. This innovative design of a photoactivated cationic polymer presents a promising and reliable strategy to achieve efficient intranasal mRNA delivery. This approach has potential applications in the development of mRNA-based vaccines for both prophylactic and therapeutic purposes.

To evaluate potential gains in outcomes from ticagrelor-based strategy according to risk stratification by Global Registry of Acute Coronary Events (GRACE) score.

Photodynamic therapy (PDT) is a widely used clinical option for tumor therapy. However, the clinical utilization of conventional small-molecule photosensitizers (PSs) for PDT has been limited by their low selectivity for disease sites, and undesirable photoactivation. To overcome these limitations, we demonstrated a tumor-specific and photoactivity-controllable nanoparticle photomedicine based on a combination of PS–biomacromolecule conjugates and polydopamine nanoparticles (PD-NP) for an effective tumor therapy. This novel photomedicine consisted of a PD-NP core and a PS-conjugated hyaluronic acid (PS-HA) shell. The PD-NP and the PS-HA play roles as a quencher for PSs and a cancer targeting moiety, respectively. The synthesized PS-HA-shielded PD-NPs (PHPD-NPs) had a relatively narrow size distribution (approximately 130 nm) with uniform spherical shapes. In response to cancer-specific intracellular enzymes (e.g., hyaluronidase), the PHPD-NPs exhibited an excellent singlet oxygen generation capacity for PDT. Furthermore, an efficient photothermal conversion ability for photothermal therapy (PTT) was also shown in the PHPD-NPs system. These properties provide superior therapeutic efficacy against cancer cells. In mice tumor model, the photoactive restorative effects of the PHPD-NPs were much higher in cancer microenvironments compared to that in the normal tissue. As a result, the PHPD-NPs showed a significant antitumor activity in in vivomice tumor model. The nanoparticle photomedicine design is a novel strategy for effective tumor therapy.

Here, antigen and adjuvant encapsulated dendritic cell‐targeted nanoparticles for immune activation in the small intestinal lymphatic system to inhibit melanoma development are described. This strategy is demonstrated using chondroitin sulfate‐coated nanoparticles (OPGMN) grafted with glycocholic acid and mannose for cationic liposomes encapsulated with ovalbumin as an antigen and polyinosine‐polycytidylic acid as a cancer‐specific adjuvant. OPGMN is absorbed in the gastrointestinal tract and delivered to the lymph nodes when orally administered. Oral delivery of OPGMN induces increased dendritic cell maturation compared to the intradermal route in the lymph node and induces T helper type 1 and type 2 responses, such as immunoglobulin G1 and G2c, interferon‐gamma, and interleukin‐2, in the blood. Repeated oral administration of OPGMN increases the population of CD3+CD8+T cells, CD44highCD62Llowmemory T cells, and CD11b+CD27+natural killer cells in the blood. OPGMN completely prevents melanoma development in the B16F10‐bearing C57BL/6 mouse model by reducing the population of CD4+CD25+Foxp3+regulatory T cells in the blood. This strategy is expected to prevent the recurrence of tumors after various cancer treatments. This study describes the nonspecific immune response and consequent inhibition of tumor formation by oral administration of bile acid‐containing ovalbumin and poly(i:c) encapsulated nanoparticles. This nanoformulation can be applied as a platform technology that provides a route through which nanoparticles containing various active ingredients can be absorbed from the small intestine and delivered to the lymph nodes.

Hepatocellular carcinoma (HCC) has one of the worst prognoses for survival as it is poorly responsive to both conventional chemotherapy and mechanism-directed therapy. This results from a lack of therapeutic concentration in the tumor tissue coupled with the highly toxic off-site effects exhibited by these compounds. Consequently, we believe the best packaging for holistic therapy for HCC will involve three components: a potent therapeutic, a rationally designed drug delivery vehicle to enrich the target site concentration of the drug, and a surface ligand that can enable a greater propensity to internalization by tumor cells compared to the parenchyma. We screened a library containing hundreds of compounds against a panel of HCC cells and found the natural product, triptolide, to be more effective than sorafenib, doxorubicin, and daunorubicin, which are the current standards of therapy. However, the potential clinical application of triptolide is limited due to its poor solubility and high toxicity. Consequently, we synthesized tumor pH-sensitive nanoformulated triptolide coated with folate for use in an HCC-subpopulation that overexpresses the folate receptor. Our results show triptolide itself can prevent disease progression, but at the cost of significant toxicity. Conversely, our pH-sensitive nanoformulated triptolide facilitates uptake into the tumor, and specifically tumor cells, leading to a further increase in efficacy while mitigating systemic toxicity.

In order to improve the anticancer effect of drug, we designed and prepared biodegradable nanogel based on all-trans retinoic acid (ATRA)/pullulan conjugate (PURA). The nanogels have 47.19–38.24 % and 1.1–1.4 % of drug loading efficiency and drug contents, respectively. The controlled drug release and zero-order drug release behavior were shown for 10 days in the PURA nanogels. In the FACS data, the cellular uptake efficiency of doxorubicin (DOX) as an anti-cancer drug in PURA nanogel was similar with that of free DOX. DOX release from PURA nanogel was facilitated in cytosol due to and the polymer degradation. The cytotoxicity of PURA was restored by the polymer degradation up to that of free DOX as same concentration. Based on these, PURA nanogel has a possible potential for effective anticancer therapy.

In order to increase the bioavailability of hydrophilic unstable drugs, polymersomes from AB3type tetra block copolymers composing of poly(ethylene glycol)-b-(3) poly(lactic acid) (EO-3LA) as a water-soluble drug delivery carrier have been investigated due to its unique properties such as high stability and high water soluble drug loading efficiency. The sizes of EO-3LA polymersomes determined by dynamic light scattering were ranged in 190–220 nm with monodispersion. Its polymeric layer with 10–20 nm at the outershell was observed by field emission scanning electron microscopy. The polymersomes showed low critical aggregation concentrations (9.2–14.9 ug/ml). Anthocyanin was employed as a model drug for unstable drug in this study. The anthocyanin loading contents of EO-3LA polymersomes are depending on PLLA content in the polymers. The high loading contents (6.6–7.0 wt%) of the polymersomes are due to their tight and rigid polymeric membranes. The polymeric membrane in EO-3LA polymersomes contributed to improve drug stability on various pHs. Moreover, this property induced sustained anthocyanin release pattern from the polymersome. Therefore, the polymersome has potential as a drug carrier for water-soluble and unstable drugs.In order to increase the bioavailability of hydrophilic unstable drugs, polymersomes from AB3type tetra block copolymers composing of poly(ethylene glycol)-b-(3) poly(lactic acid) (EO-3LA) as a water-soluble drug delivery carrier have been investigated due to its unique properties such as high stability and high water soluble drug loading efficiency. The sizes of EO-3LA polymersomes determined by dynamic light scattering were ranged in 190–220 nm with monodispersion. Its polymeric layer with 10–20 nm at the outershell was observed by field emission scanning electron microscopy. The polymersomes showed low critical aggregation concentrations (9.2–14.9 ug/ml). Anthocyanin was employed as a model drug for unstable drug in this study. The anthocyanin loading contents of EO-3LA polymersomes are depending on PLLA content in the polymers. The high loading contents (6.6–7.0 wt%) of the polymersomes are due to their tight and rigid polymeric membranes. The polymeric membrane in EO-3LA polymersomes contributed to improve drug stability on various pHs. Moreover, this property induced sustained anthocyanin release pattern from the polymersome. Therefore, the polymersome has potential as a drug carrier for water-soluble and unstable drugs.

All bound up: A poly(L‐3,4‐dihydroxyphenylalanine)‐based ligand converts hydrophobic nanoparticles into hydrophilic and biocompatible species through several binding modes. Nanoparticles functionalized with this ligand (see picture) are highly stable in various aqueous solutions. A successful in vivo MRI application using functionalized Fe3O4nanoparticles confirmed their suitability for various biomedical applications.