Codelivery of Doxorubicin and p53 Gene by ß-Cyclodextrin-Based Supramolecular Nanoparticles Formed via Host-Guest Complexation and Electrostatic Interaction.

We developed a supramolecular system for codelivery of doxorubicin (Dox) and p53 gene based on a ß-CD-containing star-shaped cationic polymer. First, a star-shaped cationic polymer consisting of a ß-CD core and 3 arms of oligoethylenimine (OEI), named CD-OEI, was used to form a supramolecular inclusion complex with hydrophobic Dox. The CD-OEI/Dox complex was subsequently used to condense plasmid DNA via electrostatic interactions to form CD-OEI/Dox/DNA polyplex nanoparticles with positive surface charges that enhanced the cellular uptake of both Dox and DNA. This supramolecular drug and gene codelivery system showed high gene transfection efficiency and effective protein expression in cancer cells. The codelivery of Dox and DNA encoding the p53 gene resulted in reduced cell viability and enhanced antitumor effects at low Dox concentrations. With its enhanced cellular uptake and anticancer efficacy, the system holds promise as a delivery carrier for potential combination cancer therapies.

Coiled-Coil Protein Hydrogels Engineered with Minimized Fiber Diameters for Sustained Release of Doxorubicin in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) lacks expressed protein targets, making therapy development challenging. Hydrogels offer a promising new route in this regard by improving the chemotherapeutic efficacy through increased solubility and sustained release. Moreover, subcutaneous hydrogel administration reduces patient burden by requiring less therapy and shorter treatment times. We recently established the design principles for the supramolecular assembly of single-domain coiled-coils into hydrogels. Using a modified computational design algorithm, we designed Q8, a hydrogel with rapid assembly for faster therapeutic hydrogel preparation. Q8 encapsulates and releases doxorubicin (Dox), enabling localized sustained release via subcutaneous injection. Remarkably, a single subcutaneous injection of Dox-laden Q8 (Q8•Dox) significantly suppresses tumors within just 1 week. This work showcases the bottom-up engineering of a fully protein-based drug delivery vehicle for improved TBNC treatment via noninvasive localized therapy.

Zinc peroxide-based nanotheranostic platform with endogenous hydrogen peroxide/oxygen generation for enhanced photodynamic-chemo therapy of tumors.

Nanotheranostic platforms, which can respond to tumor microenvironments (TME, such as low pH and hypoxia), are immensely appealing for photodynamic therapy (PDT). However, hypoxia in solid tumors harms the treatment outcome of PDT which depends on oxygen molecules to generate cytotoxic singlet oxygen (1O2). Herein, we report the design of TME-responsive smart nanotheranostic platform (DOX/ZnO2@Zr-Ce6/Pt/PEG) which can generate endogenously hydrogen peroxide (H2O2) and oxygen (O2) to alleviate hypoxia for improving photodynamic-chemo combination therapy of tumors. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite was prepared by the synthesis of ZnO2 nanoparticles, in-situ assembly of Zr-Ce6 as typical metal-organic framework (MOF) on ZnO2 surface, in-situ reduction of Pt nanozymes, amphiphilic lipids surface coating and then doxorubicin (DOX) loading. DOX/ZnO2@Zr-Ce6/Pt/PEG nanocomposite exhibits average sizes of ∼78 nm and possesses a good loading capacity (48.8 %) for DOX. When DOX/ZnO2@Zr-Ce6/Pt/PEG dispersions are intratumorally injected into mice, the weak acidic TEM induces the decomposition of ZnO2 core to generate endogenously H2O2, then Pt nanozymes catalyze H2O2 to produce O2 for alleviating tumor hypoxia. Upon laser (630 nm) irradiation, the Zr-Ce6 component in DOX/ZnO2@Zr-Ce6/Pt/PEG can produce cytotoxic 1O2, and 1O2 generation rate can be enhanced by 2.94 times due to the cascaded generation of endogenous H2O2/O2. Furthermore, the generated O2 can suppress the expression of hypoxia-inducible factor α, and further enable tumor cells to become more sensitive to chemotherapy, thereby leading to an increased effectiveness of chemotherapy treatment. The photodynamic-chemo combination therapy from DOX/ZnO2@Zr-Ce6/Pt/PEG nanoplatform exhibits remarkable tumor growth inhibition compared to chemotherapy or PDT. Thus, the present study is a good demonstration of a TME-responsive nanoplatform in a multimodal approach for cancer therapy.

Dual targetable drug delivery system based on cell membrane camouflaged liposome for enhanced tumor targeting and improved anti-tumor efficiency.

Receptor and ligand binding mediated targeted drug delivery systems (DDS) sometimes fail to target to tumor sites, and cancer cell membrane (CCM) coating can overcome the dilemma of immune clearance and nonspecific binding of DDS in vivo. In order to enhance the targeting ability and improve the anti-tumor effect, a dual targeting DDS was established based on U87MG CCM mediated homologous targeting and cyclic peptide RGD mediated active targeting. The DDS was prepared by coating RGD doped CCM onto doxorubicin (DOX) loaded liposomes. The homologous and active dual targeting ability endowed the DDS (RGD-CCM-LP-DOX) exhibited superior cancer cell affinity, improved tissue distribution and enhanced anti-tumor effects. In vivo pharmacodynamic studies revealed that RGD-CCM-LP-DOX exhibited superior therapeutic effect compared with homologous targeting CCM-LP-DOX and non-targetable LP-DOX injection. H&E staining, Ki 67 staining and TUNEL staining confirmed that RGD-CCM-LP-DOX not only increased anti-tumor efficacy, but also reduced tissue toxicity by changing the distribution in vivo. The experimental results showed that the RGD doped CCM camouflaged liposome DDS is a better choice for chemotherapeutics delivery.

A minimalist cancer cell membrane-shielded biomimetic nanoparticle for nasopharyngeal carcinoma active-targeting therapy.

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy, which is characterized by high incidence and aggression with poor diagnosis and limited therapeutic opportunity. The innovative strategy for achieving precise NPC active-targeting drug delivery has emerged as a prominent focus in clinical research. Here, a minimalist cancer cell membrane (CCM) shielded biomimetic nanoparticle (NP) was designed for NPC active-targeting therapy. Chemotherapeutant model drug doxorubicin (DOX) was loaded in polyamidoamine (PAMAM) dendrimer. The PAMAM/DOX (PD) NP was further shielded by human CNE-2 NPC CCM. Characterization results verified that the biomimetic PAMAM/DOX@CCM (abbreviated as PDC) NPs had satisfactory physical properties with high DOX-loading and excellent stability. Cell experiments demonstrated that the CNE-2 membrane-cloaked PDC NPs presented powerful cellular uptake in the sourcing cells by homologous targeting and adhesive interaction. Further in vivo results confirmed that this biomimetic nanoplatform had extended circulation and remarkable tumor-targeting capability, and the PDC NPs effectively suppressed the progression of CNE-2 tumors by systemic administration. This CCM-shielded biomimetic NP displayed a minimalist paradigm nanoplatform for precise NPC therapy, and the strategy of CCM-shielded biomimetic drug delivery system (DDS) has great potential for extensive cancer active-targeting therapy.

DNA nanodevice as a multi-module co-delivery platform for combination cancer immunotherapy.

A major challenge in combining cancer immunotherapy is the efficient delivery of multiple types of immunological stimulators to elicit a robust anti-tumor immune response and reprogram the immunosuppressive tumor microenvironment (TME). Here, we developed a DNA nanodevice that was generated by precisely assembling three types of immunological stimulators. The doxorubicin (Dox) component induced immunogenic cell death (ICD) in tumor cells and enhanced phagocytosis of antigen-presenting cells (APCs). Exogenous double-stranded DNA (dsDNA) could act as a molecular adjuvant to activate the stimulator of interferon genes (STING) signaling in APCs by engulfing dying tumor cells. Interleukin (IL)-12 and small hairpin programmed cell death-ligand 1 (shPD-L1) transcription templates were designed to regulate TME. Additionally, for targeted drug delivery, multiple cyclo[Arg-Gly-Asp-(d-Phe)-Cys] (cRGD) peptide units on DNA origami were employed. The incorporation of disulfide bonds allowed the release of multiple modules in response to intracellular glutathione (GSH) in tumors. The nanodevice promoted the infiltration of CD8+ and CD4+ cells into the tumor and generated a highly inflamed TME, thereby enhancing the effectiveness of cancer immunotherapy. Our research results indicate that the nanodevice we constructed can effectively inhibit tumor growth and prevent lung metastasis without obvious systemic toxicity, providing a promising strategy for cancer combination treatment.

Doxorubicin conjugates: a practical approach for its cardiotoxicity alleviation.

INTRODUCTION: Doxorubicin (DOX) emerges as a cornerstone in the arsenal of potent chemotherapeutic agents. Yet, the clinical deployment of DOX is tarnished by its proclivity to induce severe cardiotoxic effects, culminating in heart failure and other consequential morbidities. In response, a panoply of strategies has undergone rigorous exploration over recent decades, all aimed at attenuating DOX's cardiotoxic impact. The advent of encapsulating DOX within lipidic or polymeric nanocarriers has yielded a dual triumph, augmenting DOX's therapeutic efficacy while mitigating its deleterious side effects. AREAS COVERED: Recent strides have spotlighted the emergence of DOX conjugates as particularly auspicious avenues for ameliorating DOX-induced cardiotoxicity. These conjugates entail the fusion of DOX through physical or chemical bonds with diminutive natural or synthetic moieties, polymers, biomolecules, and nanoparticles. This spectrum encompasses interventions that impinge upon DOX's cardiotoxic mechanism, modulate cellular uptake and localization, confer antioxidative properties, or refine cellular targeting. EXPERT OPINION: The endorsement of DOX conjugates as a compelling stratagem to mitigate DOX-induced cardiotoxicity resounds from this exegesis, amplifying safety margins and the therapeutic profile of this venerated chemotherapeutic agent. Within this ambit, DOX conjugates stand as a beacon of promise in the perpetual pursuit of refining chemotherapy-induced cardiac compromise.

Preparation of Liposome Gel by Calcium Cross-Linking Induces the Long-Term Release of DOX to Improve the Antitumor Effect.

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.

Innovative gelatin-based micelles with AS1411 aptamer targeting and reduction responsiveness for doxorubicin delivery in tumor therapy.

Herein, we constructed innovative reduction-sensitive and targeted gelatin-based micelles for doxorubicin (DOX) delivery in tumor therapy. AS1411 aptamer-modified gelatin-ss-tocopherol succinate (AGSST) and the control GSST without AS1411 modification were synthesized and characterized. Antitumor drug DOX-containing AGSST (AGSST-D) and GSST-D nanoparticles were prepared, and their shapes were almost spherical. Reduction-responsive characteristics of DOX release in vitro were revealed in AGSST-D and GSST-D. Compared with non-targeted GSST-D, AGSST-D demonstrated better intracellular uptake and stronger cytotoxicity against nucleolin-overexpressed A549 cells. Importantly, AGSST-D micelles showed more effective killing activity in A549-bearing mice than GSST-D and DOX⋅HCl. It was revealed that AGSST-D micelles had no obvious systemic toxicity. Overall, AGSST micelles would have the potential to be an effective drug carrier for targeted tumor therapy.

Application of Doxorubicin-loaded PLGA nanoparticles targeting both tumor cells and cancer-associated fibroblasts on 3D human skin equivalents mimicking melanoma and cutaneous squamous cell carcinoma.

Nanoparticle (NP) use in cancer therapy is extensively studied in skin cancers. Cancer-associated fibroblasts (CAFs), a major tumor microenvironment (TME) component, promote cancer progression, making dual targeting of cancer cells and CAFs an effective therapy. However, dual NP-based targeting therapy on both tumor cells and CAFs is poorly investigated in skin cancers. Herein, we prepared and characterized doxorubicin-loaded PLGA NPs (DOX@PLGA NPs) and studied their anti-tumor effects on cutaneous melanoma (SKCM)(AN, M14) and cutaneous squamous cell carcinoma (cSCC) (MET1, MET2) cell lines in monolayer, as well as their impact on CAF deactivation. Then, we established 3D full thickness models (FTM) models of SKCM and cSCC using AN or MET2 cells on dermis matrix populated with CAFs respectively, and assessed the NPs' tumor penetration, tumor-killing ability, and CAF phenotype regulation through both topical administration and intradermal injection. The results show that, in monolayer, DOX@PLGA NPs inhibited cancer cell growth and induced apoptosis in a dose- and time-dependent manner, with a weaker effect on CAFs. DOX@PLGA NPs reduced CAF-marker expression and had successful anti-tumor effects in 3D skin cancer FTMs, with decreased tumor-load and invasion. DOX@PLGA NPs also showed great delivery potential in the FTMs and could be used as a platform for future functional study of NPs in skin cancers using human-derived skin equivalents. This study provides promising evidence for the potential of DOX@PLGA NPs in dual targeting therapy for SKCM and cSCC.

Targeted co-delivery of FOXM1 aptamer and DOX by nucleolin aptamer-functionalized pH-responsive biocompatible nanodelivery system to enhance therapeutic efficacy against breast cancer: in vitro and in vivo.

Targeted nanodelivery systems offer a promising approach to cancer treatment, including the most common cancer in women, breast cancer. In this study, a targeted, pH-responsive, and biocompatible nanodelivery system based on nucleolin aptamer-functionalized biogenic titanium dioxide nanoparticles (TNP) was developed for targeted co-delivery of FOXM1 aptamer and doxorubicin (DOX) to improve breast cancer therapy. The developed targeted nanodelivery system exhibited almost spherical morphology with 124.89 ± 12.97 nm in diameter and zeta potential value of - 23.78 ± 3.66 mV. FOXM1 aptamer and DOX were loaded into the nanodelivery system with an efficiency of 100% and 97%, respectively. Moreover, the targeted nanodelivery system demonstrated excellent stability in serum and a pH-responsive sustained drug release profile over a period of 240 h following Higuchi kinetic and Fickian diffusion mechanism. The in vitro cytotoxicity experiments demonstrated that the targeted nanodelivery system provided selective internalization and strong growth inhibition effects of about 45 and 51% against nucleolin-positive 4T1 and MCF-7 breast cancer cell lines. It is noteworthy that these phenomena were not observed in nucleolin-negative cells (CHO). The preclinical studies revealed that a single-dose intravenous injection of the targeted nanodelivery system into 4T1-bearing mice inhibited tumor growth by 1.7- and 1.4-fold more efficiently than the free drug and the non-targeted nanodelivery system, respectively. Our results suggested that the developed innovative targeted pH-responsive biocompatible nanodelivery system could serve as a prospectively potential platform to improve breast cancer treatment.

Calidad de vida en pacientes con tumor vesical no músculo-invasivo sometidos a tratamiento adyuvante intravesical / Quality of life in patients with non-muscle invasive bladder tumor undergoing adjuvant intravesical treatment

Introducción El objetivo del estudio fue establecer posible relación entre los tratamientos con mitomicina-C (MMC) y bacilo de Calmette-Guérin (BCG) y la afectación en la calidad de vida. Material y métodos Estudio cuasiexperimental, prospectivo y longitudinal, recogiendo pacientes sometidos a tratamiento adyuvante en TVNMI. Se utilizaron los cuestionarios Short form-12 (SF-12) y Urogenital Distress Inventory-6 (UDI-6) para medir la calidad de vida. Se compararon las puntuaciones de los cuestionarios entre casos con MMC y BCG antes de iniciar la inducción (M1), a las 4 semanas (M2) y a los dos meses (M3). Resultados Se recogieron 90 pacientes, 54 en el grupo de BCG y 36 en el de MMC. Se comprobó que los pacientes con BCG percibían peor calidad de vida física comparados con los de MMC en M2 (OR:2,59, p=0,046). Además, se hallaron cambios significativos en la calidad de vida urinaria de los pacientes en tratamiento con MMC entre los diferentes momentos temporales (puntuación del UDI-6: 33,33 en M1, 27,78 en M2 y 16,67 en M3, p=0,001). Conclusiones No existen diferencias en la calidad de vida urinaria entre los pacientes tratados con MMC y BCG. Los pacientes con MMC muestran una recuperación significativa de la calidad de vida urinaria a partir de la finalización de la inducción, que aumenta aún más a los dos meses de la misma. Además, los pacientes tratados con BCG presentan peor calidad de vida física a las 4 semanas de tratamiento que aquellos tratados con MMC (AU)

Introduction The objective of the study was to establish a possible relationship between mitomycin-C (MMC) and bacillus Calmette-Guérin (BCG) treatments and quality of life impairment. Material and methods Quasi-experimental, prospective, and longitudinal study including patients undergoing adjuvant treatment in NMIBC. The Short form-12 (SF-12) and Urogenital Distress Inventory-6 (UDI-6) questionnaires were used to measure quality of life. Questionnaire scores were compared between cases with MMC and BCG before induction (M1), at 4 weeks (M2) and at 2 months (M3). Results Of the 90 patients enrolled, 54 were in the BCG group and 36 in the MMC group. It was found that BCG patients had worse perceived physical quality of life compared to MMC patients in M2 (OR:2.59, p=0.046). In addition, significant changes were found in the urinary quality of life of patients on MMC treatment between the different time points (UDI-6 score: 33.33 in M1, 27.78 in M2 and 16.67 in M3, p=0.001). Conclusions There are no differences in urinary quality of life between patients treated with MMC and BCG. Patients with MMC show a significant recovery of urinary quality of life from the completion of the induction course, which becomes even more significant after 2 months. In addition, BCG-treated patients have worse physical quality of life after 4 weeks of treatment than those treated with MMC (AU)

Efecto de la mitomicina en comparación con la gemcitabina intravesical en el tratamiento del cáncer de vejiga sin invasión muscular: metaanálisis / Effect of intravesical mitomycin compared with gemcitabine on the treatment non-muscle invasive bladder cancer: A meta-analysis

Introducción Se realizó un metaanálisis para evaluar el efecto de la mitomicina intravesical en comparación con la gemcitabina en el tratamiento del cáncer de vejiga sin invasión muscular. Métodos Se realizó una búsqueda bibliográfica sistemática hasta noviembre de 2021 y 6 estudios incluyeron 389 sujetos con cáncer de vejiga no invasivo al músculo al inicio del estudio; 197 de ellos recibieron mitomicina intravesical y 192 gemcitabina intravesical. Se informó de las relaciones sobre el efecto de la mitomicina intravesical en comparación con la gemcitabina en el tratamiento del cáncer de vejiga no invasivo al músculo. Se calculó la odds ratio (OR) con intervalos de confianza (IC) del 95% para evaluar el efecto de la mitomicina en comparación con el de la gemcitabina intravesical en el tratamiento del cáncer de vejiga no invasivo mediante el método dicotómico con un modelo de efectos aleatorios o fijos. Resultados La mitomicina intravesical obtuvo tasas significativamente mayores de recidiva (OR: 2,41; IC 95%: 1,43-4,08; p=0,001) y de cistitis química (OR: 4,39; IC 95%: 2,27-8,51; p<0,001) en comparación con la gemcitabina intravesical en sujetos con cáncer de vejiga no invasivo. Sin embargo, la mitomicina intravesical no mostró diferencias significativas en su efecto sobre la hematuria (OR: 1,71; IC 95%: 0,68-4,33; p=0,26), reacciones cutáneas (OR, 2,04; IC 95%: 0,59-7,07; p=0,26) y daños en la función hepática y renal (OR, 1,96; IC 95%; 0,35-10,96; p=0,44) en comparación con la gemcitabina intravesical en sujetos con cáncer de vejiga no invasivo al músculo. Conclusiones La mitomicina intravesical tuvo tasas de recidiva y cistitis química significativamente mayores y no hubo diferencias significativas en su efecto sobre la hematuria, la reacción cutánea y el daño de la función hepática y renal en comparación con la gemcitabina intravesical en sujetos con cáncer de vejiga no invasivo al músculo. Se necesitan más estudios para validar estos resultados (AU)

Introduction We performed a meta-analysis to evaluate the effect of intravesical mitomycin compared with gemcitabine on the treatment of non-muscle invasive bladder cancer. Methods A systematic literature search up to November 2021 was done and 6 studies included 389 subjects with non-muscle invasive bladder cancer at the start of the study; 197 of them were provided with intravesical-mitomycin and 192 with intravesical gemcitabine. The studies reported the relationships about the effect of intravesical mitomycin compared with gemcitabine on the treatment of non-muscle invasive bladder cancer. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) to assess the effect of intravesical mitomycin compared with gemcitabine on the treatment of non-muscle invasive bladder cancer using the dichotomous method with a random or fixed-effect model. Results Intravesical mitomycin had significantly higher recurrence rates (OR, 2.41; 95% CI, 1.43-4.08, P=.001) and chemical cystitis (OR, 4.39; 95% CI, 2.27-8.51, P<.001) compared to intravesical gemcitabine in subjects with non-muscle invasive bladder cancer. However, intravesical mitomycin had no significant difference in its effect on hematuria (OR, 1.71; 95% CI, .68-4.33, P=.26), skin reaction (OR, 2.04; 95% CI, .59-7.07, P=.26), and liver and kidney functions damage (OR, 1.96; 95% CI, 0.35-10.96, P=.44) compared to intravesical gemcitabine in subjects with non-muscle invasive bladder cancer. Conclusions Intravesical mitomycin had significantly higher recurrence rates and chemical cystitis and no significant difference in its effect on hematuria, skin reaction, and liver and kidney functions damage compared to intravesical gemcitabine in subjects with non-muscle invasive bladder cancer. Further studies are required to validate these findings (AU)

The clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C after transurethral resection of bladder tumour in patients with nonmuscular invasive bladder cancer: A meta-analysis.

BACKGROUND: This review and meta-analysis aimed to systematically evaluate the clinical efficacy and safety of equipment-assisted intravesical instillation of mitomycin C (MMC) in patients with nonmuscular invasive bladder cancer (NMIBC) after transurethral resection of bladder tumour (TURBT). METHODS: The Embase, PubMed, CNKI, CBM, WANGFANG, VIP, Cochrane Library, and Clinicaltrial.com databases were searched for articles published before April 2022. The experimental group was treated with intravesical instillation of MMC assisted by equipment, including radiofrequency-induced thermochemotherapy, conductive thermochemical therapy, electromotive drug administration, or locoregional hyperthermia. The control group was treated with simple MMC perfusion. The outcomes of interest in the meta-analysis were recurrence, progression, side-effects, gross haematuria, and bladder irritation. RESULTS: A total of 15 studies that enrolled 1,190 patients were included in the meta-analysis. Compared to that of the control group, device-assisted intravesical instillation of MMC significantly reduced both tumour recurrence (odds ratio [OR] = 0.32, 95% confidence interval [CI] [0.24, 0.42], P <0.00001) and progression (OR = 0.29, 95% CI [0.12, 0.67], P = 0.004). There were no significant differences between the two groups in terms of safety (OR = 1.21, 95% CI [0.66,2.21], P = 0.54), bladder irritation (OR = 1.06, 95% CI [0.72,1.55], P = 0.78), or gross haematuria (OR = 1.11, 95% CI [0.64,1.94], P = 0.72). CONCLUSIONS: Equipment-assisted intravesical instillation of MMC significantly reduced the recurrence and progression of patients with NMIBC who underwent TURBT and improved their quality of life. Given the significant heterogeneity in research quality and sample size among earlier studies, more prospective, multicentre, large sample randomized controlled trials are needed to supplement and verify this in the future.

Epiteliopatía progresiva en ondas tras neoplasia intraepitelial conjutival. Caso clínico atípico / Advancing wavelike epitheliopathy after conjunctival intraepithelial neoplasia. Atypical case report

Se presenta un caso atípico de epiteliopatía progresiva en ondas consecutiva a tratamiento tópico de una neoplasia intraepitelial conjuntival en 360°. Se usaron colirios de mitomicina (0,2mg/ml) e interferón (1MUI/ml). Presentación atípica con foco limbar principal migratorio, y no claramente delimitado en su sitio horario a través de su evolución. Tratado con flurometolona y lágrimas artificiales, con resultado de resolución completa (AU)

An atypical Advancing Wavelike Epitheliopathy case, consecutive to topical treatment for a 360° Conjunctival Intraepithelial Neoplasia, is presented. Mitomycin (0.2mg/ml) and interferon (1MUI/ml) drops were used. An atypical presentation, with migrating limbal focus, non clearly delimited in its hourly site through its evolution. Treated with flurometholone drops plus artificial tears, working to complete resolution (AU)

Extending Treatment Intervals of R-CHOP Therapy Might Be Acceptable for Some Patients with Non-indolent Non-Hodgkin's B-cell Lymphoma.

R-CHOP therapy is generally performed every 3 weeks. We investigated the effects of extending the interval of R-CHOP therapy for > 1 week on the prognoses of patients with non-indolent non-Hodgkin's B-cell lymphoma. Among the 338 patients with non-indolent non-Hodgkin's B-cell lymphoma who received initial chemotherapy at our institution, we focused on 178 patients who received R-CHOP therapy and analyzed the outcomes of the patients stratified by the treatment intervals. The estimated 3-year overall survival (OS) for the entire population was 82.1%. Patients treated at intervals of ≥ 4 weeks were significantly older, and they had significantly longer follow-up periods and lower relative dose intensity. But the estimated 3-year OS was comparable to those treated at <4 weeks (83.3% vs. 80.5% p=0.947). In a multivariate analysis, age and the dose of anti-cancer agents had significant impacts on OS, but there was no significant relationship regarding the treatment intervals. Propensity score matching confirmed the same result. R-CHOP therapy every around 4 weeks could achieve relatively good survival in some selected patients with non-indolent non-Hodgkin's B-cell lymphoma.

Radiotherapy-induced enrichment of EGF-modified doxorubicin nanoparticles enhances the therapeutic outcome of lung cancer.

Chemotherapy is the primary treatment for advanced non-small-cell lung cancer (NSCLC). However, related dose-dependent toxicity limits its clinical use. Therefore, it is necessary to explore new strategies for improving the clinical outcomes while reducing the side effects of chemotherapy in the treatment of NSCLC. In this study, we designed and synthesized epidermal growth factor (EGF)-modified doxorubicin nanoparticles (EGF@DOX-NPs) that selectively targets the epidermal growth factor receptor (EGFR) overexpressed in lung tumor cells. When administered in combination with low-dose X-ray radiotherapy (RT), the NPs preferentially accumulated at the tumor site due to radiation-induced outburst of the local intra-tumoral blood vessels. Compared with DOX alone, EGF@DOX-NPs significantly decreased the viability and migration and enhanced the apoptosis rates of tumor cells in vitro. Also, the EGF@DOX-NPs significantly inhibited tumor growth in vivo, increasing the survival of the tumor-bearing mice without apparent systemic toxic effects through RT-induced aggregation. The tumor cell proliferation was greatly inhibited in the RT + EGF@DOX-NPs group. Contrarily, the apoptosis of tumor cells was significantly higher in this group. These results confirm the promising clinical application of radiotherapy in combination with EGF@DOX-NPs for lung cancer treatment.

Multifunctional liposome for photoacoustic/ultrasound imaging-guided chemo/photothermal retinoblastoma therapy.

Retinoblastoma (RB) is a malignant intraocular neoplasm that occurs in children. Diagnosis and therapy are frequently delayed, often leading to metastasis, which necessitates effective imaging and treatment. In recent years, the use of nanoplatforms allowing both imaging and targeted treatment has attracted much attention. Herein, we report a novel nanoplatform folate-receptor (FR) targeted laser-activatable liposome termed FA-DOX-ICG-PFP@Lip, which is loaded with doxorubicin (DOX)/indocyanine green (ICG) and liquid perfluoropentane (PFP) for photoacoustic/ultrasound (PA/US) dual-modal imaging-guided chemo/photothermal RB therapy. The dual-modal imaging capability, photothermal conversion under laser irradiation, biocompatibility, and antitumor ability of these liposomes were appraised. The multifunctional liposome showed a good tumor targeting ability and was efficacious as a dual-modality contrast agent both in vivo and in vitro. When laser-irradiated, the liposome converted light energy to heat. This action caused immediate destruction of tumor cells, while simultaneously initiating PFP phase transformation to release DOX, resulting in both photothermal and chemotherapeutic antitumor effects. Notably, the FA-DOX-ICG-PFP@Lip showed good biocompatibility and no systemic toxicity was observed after laser irradiation in RB tumor-bearing mice. Hence, the FA-DOX-ICG-PFP@Lip shows great promise for dual-modal imaging-guided chemo/photothermal therapy, and may have significant value for diagnosing and treating RB.

Synergic fabrication of multifunctional liposomes nanocomposites for improved radiofrequency ablation combination for liver metastasis cancer therapy.

The field of biomedical research has recently been interested in nanoplatforms with various functionalities, such as cancer drug carriers and MRI and optical imaging, as well as thermal treatment, among other things. As a result of the present investigation, a unique multifunctional liposome (MFL) was established in this investigation. Using radiofrequency-induced imaging and drug release based on magnetic field impact, a dual drug delivery targeted with tumor multi-mechanism treatment was made more effective. The C60 (fullerene) surface was coated with iron nanocomposites to establish the proposed nanosystems, and PEGylation was used (Fe3O4-C60-PEG2000). For fullerene radiofrequency-triggered drug release, thermosensitive DPPC liposomes with folate-DSPE-PEG2000 enveloped the binary nanosystems and doxorubicin (DOX). The in vitro cytotoxicity of the nanocomposites was confirmed by the liver metastasis in HT-29 colon cancer cells using radiofrequency. The flow cytometry analysis confirmed the apoptosis cell death mechanism. The thermal treatment combined chemotherapeutic MFL nano framework transformed radiofrequency radiation from thermoresponsive liposomes, which was noticed both in vivo and in vitro. Due to their superior active tumor targeting and magnetic targeting characteristics, the MFL could also selectively destroy cancerous liver cells in highly co-localized targets.

Pharmacodynamics and pharmacokinetics of PLGA-based doxorubicin-loaded implants for tumor therapy.

The traditional systemic chemotherapy through intravenous infusion of doxorubicin (DOX) has many side effects. The aim of this study was to develop a PLGA-based DOX-loaded implant and to evaluate the efficacy and drug metabolism distribution of the implant in intratumoral chemotherapy for osteosarcoma (OS). In this study, implants containing DOX, poly(d,l-lactide-co-glycolide), and polyethylene glycol 4000 were prepared by melt-molding method. Then, the antitumor activity and systemic drug distribution of the implants were tested in a K7M2 OS bearing mouse model. The scanning electron microscope images showed that DOX was uniformly dispersed in the polymer matrix. Both the in vitro and in vivo release profiles of implants are characterized by three-phase release. Implantation of DOX-loaded implants into tumors can inhibit tumor growth in a dose-dependent manner. The pharmacokinetic behavior shows that intratumor chemotherapy through implants has a much higher drug concentration in tumors than in normal tissues, which may be the reason for improving antitumor activity and reducing systemic side effects. In summary, the drug release of the implants prepared in this study is sustained and stable, which promotes long-term local accumulation of drugs in tumors, improves the efficacy of chemotherapy and has low toxicity to normal tissues.