3-dimensional ultrasound-guided percutaneous nephrolithotomy: total free versus partial fluoroscopy.

PURPOSE: To provide a comprehensive analysis about safety and efficacy of fluoroscopy-free total ultrasound-guided percutaneous nephrolithotomy (TUPN) versus ultrasound with fluoroscopy-guided percutaneous nephrolithotomy (UFPN). PATIENTS AND METHODS: 3-dimensional ultrasound-guided PCNL was retrospectively analyzed in 377 patients from 2015 to 2017. TUPN was performed in 185 patients and UFPN was finished in 192 patients. In TUPN group, the entire procedures of puncture and dilation were real-time monitored by three-dimensional ultrasound alone. Conversely, in UFPN group, the puncture was performed under the guidance of real-time ultrasound, while the dilation was monitored by fluoroscopy. Preoperative demographic data, intraoperative parameters and postoperative complications were compared. RESULTS: Groups were comparable in baseline characteristics. Fifty percent of patients were Guy's score III-IV and over half of the patients were mild or none of hydronephrosis. All renal punctures were successfully performed. The primary successful rates of dilation were more than 95% in both groups (95.1% in TUPN and 95.8% in UFPN, p = 0.74). Two or more accesses were established in 33 patients (17.8%) in TUPN group and 25 patients (13%) in UFPN group (p = 0.20). Post-operative instant stone-free rates were 88.6% and 90.1%, TUPN versus UFPN, respectively, p = 0.65. Most of the complications were minor and there were no differences in Clavien-Dindo complications in both groups. Mean operating time and hospitalization were comparable. CONCLUSIONS: Our findings show that fluoroscopy-free total ultrasound-guided PCNL represents an alternatively safe and efficient approach for the treatment of renal stones. Further study will be required to evaluate fluoroscopy-free TUPN in various clinical settings.

Rare adrenal gland incidentaloma: an unusual Ewing's sarcoma family of tumor presentation and literature review.

BACKGROUND: Members of the Ewing's sarcoma family of tumor (ESFT) are malignant neoplasms and rarely observed in the adrenal gland. CASE PRESENTATION: We report an extremely exceptional case of ESFT rising from the adrenal gland in a 57-year-old Chinese man. The patient was hospitalized with abdominal swelling for 2 months. Computed tomography (CT) scan revealed a nearly-circular mass measuring about 8.1 × 10.6 cm in the right adrenal region. The patient underwent right adrenal resection. Histopathologic examination found the tumor was composed of small round blue cells forming typical Homer-Wright rosettes in focal area. The immunohistochemical analysis confirmed the case to be ESFT, which was positive for membranous CD99 and nuclear FLI-1. The patient was scheduled for four courses of large doses of chemotherapy and died for cancer metastasis one year later after surgery. CONCLUSIONS: Histopathological evidence of Homer-Wright rosettes and immunohistochemical markers positivity, such as CD99 and FLI-1, are valuable factors for ESFT diagnosis, although cytogenetic analysis is considered as the gold standard. Complete surgery is the treatment of choice for ESFT and adjuvant radiotherapy and combination chemotherapy can significantly improve the survival rate of postoperative patients.

A Nanostructured Degradable Ureteral Stent Fabricated by Electrospinning for Upper Urinary Tract Reconstruction.

A degradable polycaprolactone(PCL)/poly(lactic-co-glycolic acid, LA:GA = 80:20) (PLGA) ureter tubular stent was fabricated by electrospinning. The structure and properties of the stents were investigated by the mechanical property testing, scanning electron microscopy (SEM), degradability test in vitro and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The stent was transplanted to the dorsal muscle of rabbit to evaluate its tissue compatibility. It was shown that the stent has the nano-structure. The mechanical test showed that with the increase in PCL concentration, the mechanical properties of the stent gradually increased, and it could meet the demands of a urethral stent. The collapse time of different concentration of PCL/PLGA (5%, 15%, and 25%) was 28, 42, and 56 days, respectively. These results provide strong evidence that the degradation time can be increased with the increase in PCL concentration. The results of the MTT assay show that the PCL/PLGA stent had no cytotoxicity. In muscle implantation tests, acute tissue reactions due to operation trauma were seen in all specimens at 1 week. After four weeks, the number of inflammatory cells had decreased significantly. Only a few inflammatory cells were seen in the PCL/PLGA stent group after 12 weeks, and the foreign body reaction was more severe in the control group. Animal orthotopic transplantation experiments of these ureteral stents will be done to evaluate its degradable model and tissue compatibility.

The effects of STAT3 and Survivin silencing on the growth of human bladder carcinoma cells.

Despite accumulating evidence suggesting a critical role of signal transducer and activator of transcription 3 (STAT3) and Survivin in human bladder cancer, the effects of silencing these genes on the proliferation of T24 bladder carcinoma cells remain unknown. Here, we investigated the inhibitory effects of STAT3 or Survivin silencing on the in vitro and in vivo growth of human T24 bladder carcinoma cells. Small interfering RNA (siRNA) vectors targeting STAT3, Survivin, or both genes were designed and synthesized. The recombinant plasmid DNA constructs were confirmed by DNA sequencing. They were then transiently transfected into T24 cells, and the mRNA and protein expressions of STAT3 and Survivin were determined using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot, respectively. Cell proliferation was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The in vivo growth-inhibition effects of the siRNA vectors were assessed using a bladder cancer mouse model. The tumor weight and size was recorded 4 weeks post-inoculation. We successfully synthesized four siRNA vectors targeting STAT3 and four vectors targeting Survivin. The STAT3-3 and Survivin-4 siRNA constructs were most efficient in reducing STAT3 or Survivin expression, respectively. We then constructed a vector containing these two sequences together (STAT3-Survivin siRNA) and found that the single vector efficiently silenced STAT3 and Survivin expression. Moreover, silencing of STAT3 or Survivin significantly suppressed the in vitro and in vivo proliferation of T24 cells compared to the controls (P<0.05). Our findings indicated that the downregulation of STAT3 or Survivin can suppress the proliferation of T24 bladder cancer cells. Moreover, no additive effects were observed when STAT3 and Survivin were knocked down together, suggesting that they work in the same signaling pathway in T24 cells. These results provide valuable insights into understanding the pathways involved during the tumorigenesis of bladder cancer.

Standard-tract combined with mini-tract in percutaneous nephrolithotomy for renal staghorn calculi.

PURPOSE: To compare the safety and efficacy of standard-tract combined with mini-tract to single standard-tract in percutaneous nephrolithotomy (PCNL) for renal staghorn calculi. METHODS: The records of 216 patients with staghorn calculi (110 (50.9%) had complete and 106 (49.1%) had partial) who received PCNL were reviewed retrospectively. 58 patients received standard-tract combined with mini-tract PCNL (group A) and 158 patients underwent single standard-tract PCNL (group B). Both groups had comparable demographic data. Operation time, stone-free rate, blood transfusion rate, hospital stay and complications were analyzed. RESULTS: Postoperative Clavien score in the two groups was similar. The rate of blood transfusion and perioperative bleeding requiring superselective embolization were not statistically significant between the groups (p = 0.557, 0.463, respectively). The mean operation time was comparable between groups in the standard-tract combined with mini-tract group. The stone-free rate was significantly higher (89.7 vs. 78.5%, p = 0.044) in group A than in group B. The rate of second PCNL was higher in group B. CONCLUSION: The standard-tract combined with mini-tract results had higher success rates with no increase in the incidence of complications, and should be the first option for renal staghorn calculi.

Causality of genetically determined metabolites on susceptibility to prevalent urological cancers: a two-sample Mendelian randomization study and meta-analysis.

Background: Prevalent urological cancers, including kidney, prostate, bladder, and testicular cancers, contribute significantly to global cancer incidence and mortality. Metabolomics, focusing on small-molecule intermediates, has emerged as a tool to understand cancer etiology. Given the knowledge gap in this field, we employ a two-sample Mendelian randomization (MR) analysis to investigate the causal relationships between genetically determined metabolites (GDMs) and the susceptibility to four common urological cancers. Methods: The study employs genome-wide association studies (GWAS) data from European populations, featuring the most extensive case count available for both blood metabolites and four prevalent urological cancers. Preliminary and secondary MR analyses were separately conducted, employing inverse variance weighted (IVW) as the primary method. Multiple statistical analyses, including the MR-Steiger test, Cochran's Q test, leave-one-out analysis, MR-Egger intercept analysis, and MR-PRESSO analysis, were executed to ensure robustness. Additionally, a meta-analysis was carried out to consolidate findings. The weighted median (WM) method was utilized for a relatively lenient correction (PWM < 0.05). Results: After rigorous genetic variation filtering, 645 out of 1,400 metabolites were included in both preliminary and secondary MR analyses. Preliminary MR analysis identified 96 potential causal associations between 94 distinct metabolites and four urological cancers. Secondary analysis based on Finnish outcome data revealed 93 potential causal associations. Cross-database meta-analysis identified 68 blood metabolites associated with four urological cancers. Notably, 31 metabolites remained significant after using WM for correction, with additional 37 suggestive causal relationships. Reverse MR analysis revealed a significant causal association between genetically predicted prostate cancer and elevated 4-hydroxychlorothalonil levels (IVW, combined OR: 1.039, 95% CI 1.014-1.064, p = 0.002; WM, combined OR: 1.052, 95% CI 1.010-1.095, p = 0.014). Conclusion: This comprehensive MR study provides insights into the causal relationships between blood metabolites and urological cancers, revealing potential biomarkers and therapeutic targets, thereby addressing gaps in understanding and laying the foundation for targeted interventions in urological cancer research and treatment.

Prone versus modified supine position in percutaneous nephrolithotomy: a prospective randomized study.

OBJECTIVE: To perform a prospective randomized trial comparing the efficacy and safety of percutaneous nephrolithotomy (PCNL) in the prone and modified supine positions. METHODS: Between August 2010 and August 2011, 102 patients with renal calculi and 20 patients with ureteral calculi were randomized to undergo fluoroscopy and ultrasound-guided PCNL procedures in the prone or modified supine position. Baseline characteristics, puncture position, numbers of punctures, operation time, stone free rate, loss of blood, hospital stay and second phase PCNL were compared in the two groups. RESULTS: There were no significant differences in gender, age, body mass index, stone location, stone size and the presence of hydronephrosis between the two groups. The rate of second PCNL was significantly higher and the stone clearance rate was significantly lower in the modified supine than in the prone position group. Mean operation time was significantly lower in the prone than in the modified supine position group (78 min vs 88 min, P<0.05). There were no significant differences in rates of rib and calyx puncture, numbers of punctures, mean blood loss, and mean hospital stay between the two groups. CONCLUSIONS: Both the prone and modified supine positions are effective and safe for PCNL. Operation time was longer in the modified supine group, and patients undergoing PCNL in the modified supine position more frequently required a second operation due to a lower stone clearance rate.

Doppler ultrasound and X-ray-guided percutaneous nephrolithotomy with one-step balloon dilation for complex renal stones.

OBJECTIVES: To assess the safety and efficacy of combining Doppler ultrasound with X-ray-guided percutaneous nephrolithotomy (PCNL) with one-step balloon dilation for management of complex renal stones. MATERIAL AND METHODS: We retrospectively analyzed 85 renal stone patients who underwent 89 PCNLs from January 2011 to May 2012. Doppler ultrasound with X-ray-guided PCNL with one-step balloon dilation was finished on the Fluoroscopic Table (Siemens, Berlin, Germany) with the patient under general anesthesia. RESULTS: The study included 85 patients (49 male and 36 female) with a mean age of 42.5 ± 16.4 years. All patients underwent 89 PCNLs (4 patients had bilateral stones). The mean operative time was 72.8 min (range: 35-140). The average fluoroscopic screening time was 5.55 ± 1.81 s (range: 4-12). Successful access to the collecting system was 98.9% (88/89). Although most of the cases (85/89) were managed satisfactorily by a single tract, a second tract was used in 4 cases. No severe complications occurred. The stone-free rate of PCNL monotherapy was 77.5% (69/89). At 3 months, the stone-free rate increased to 89.9% (80/89) after shock wave lithotripsy. CONCLUSIONS: PCNL with one-step balloon dilation for the management of complex renal stones under the guidance of combining Doppler ultrasound with X-ray is safe and effective because of its high stone-free rate and low operative time.

Adverse events in patients with advanced urothelial carcinoma treated with erdafitinib: a retrospective pharmacovigilance study.

Purpose: On 12 April 2019, erdafitinib gained the first FDA approval as the second-line treatment for adult patients with locally advanced or metastatic urothelial cancer following progression during or after at least one previous line of platinum-based chemotherapy. However, the long-term safety profile of erdafitinib in a large patient population remains unexplored. The current study aimed to assess the adverse events (AEs) associated with erdafitinib through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Method: The reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms based on disproportionality were employed to quantify the signals of erdafitinib-associated AEs. Results: A total of 6,322,279 reports of AEs were retrieved from the FAERS database spanning 2019 to 2022, out of which, 700 reports of erdafitinib as the "primary suspected" were identified. These erdafitinib-induced AEs were observed across 24 targeted system organ classes (SOCs). After conforming to the four algorithms at the same time, a total of 441 signals of erdafitinib-induced AEs were detected across 23 SOCs. Notably, signals associated with metabolism and nutrition disorders, eye disorders, and skin and subcutaneous tissue disorders were among the most prevalent. The median onset time for AEs was found to be 54 days [interquartile range (IQR) 17-112 days], with a majority of AEs occurring within the initial 6 months after initiating erdafitinib (37.23% within the first month, 15.53% within the second month, and 16.79% within the third month). Conclusion: The findings of this study align with existing clinical observations, offering a comprehensive long-term post-marketing safety evaluation of erdafitinib. The results provide valuable evidence to enhance the understanding of erdafitinib's safety profile, aiding further research and guiding clinical practice.

Super-stiff guidewire or loach guidewire during percutaneous nephrolithotomy?

Objectives: The objectives of this work are to compare the outcomes between loach guidewire and super-stiff guidewire during percutaneous nephrolithotomy (PCNL) and find potential indications of different guidewires. Patients and methods: We retrospectively reviewed our institutional PCNL database from 2017 to 2021. Patients who underwent PCNL guided by loach guidewire were assigned to group A (489 patients); patients who received super-stiff guidewire were assigned to group B (269 patients). Preoperative demographic data, intraoperative parameters, and postoperative complications were compared. The conditions and reasons of failed placement of guidewire needed readjustment were evaluated as well. Results: Preoperative demographic data and most intraoperative parameters were not statistically different between the groups. Postoperative Clavien-Dindo complications were also comparable, with low rate of complications. However, failed placement of guidewire more occurred in group A (8.2% vs. 4.0%, respectively, p = 0.03). Compared with the super-stiff guidewire, the loach guidewire was easier pass/slip into any place either it be perinephric or blood vessels. In most failed group A cases and all failed group B cases, the guidewire was placed in the perirenal fat. Six patients (15%) in group A, the guidewires entered into vessels. Conclusions: Our results support that the faulty placement of loach guidewire is significantly more common compared with super-stiff guidewire. Double confirmation is needed to prevent a major complication out of wrong dilatation whenever there is doubt about the wrong location of the guidewire.

Primary clear cell adenocarcinoma of the bladder with recurrence: a case report and literature review.

Clear cell carcinoma of the bladder is a rare tumor of the bladder. There are few reports available on this rare disease, and no cases with recurrence were reported. Here we present a case of 68-year-old woman with primary clear cell carcinoma of the bladder, who underwent repeat TUR-BT and tumor recurrence. We also reviewed the previous treatments and prognoses in previous case reports and evaluate the proper treatment for this disease. Once the diagnosis is determined, the radical surgery should be recommended. The recurrence is not prevented based on post-TUR intravesical therapy.

Post-percutaneous nephrolithotomy septic shock and severe hemorrhage: a study of risk factors.

OBJECTIVE: To identify the risk factors predicting septic shock and severe hemorrhage in percutaneous nephrolithotomy (PCNL). METHODS: We retrospectively analyzed 420 renal calculi patients who underwent ultrasound-guided PCNL from March 2005 to May 2011. Data on patients who experienced infectious shock requiring anti-shock therapy and severe renal bleeding requiring angiographic renal embolization or nephrectomy were compared with other patients using univariate analyses. RESULTS: Of 420 patients, 10 (2.4%) suffered septic shock and 4 (1%) had severe hemorrhage. The two significant risk factors for infectious shock were preoperative urine white blood cell count and operation time. For severe bleeding the absence of hydronephrosis and puncture time were significant risk factors. Operation time >90 min was associated with both septic shock and severe renal bleeding (p = 0.017). In contrast, the risk of encountering severe renal bleeding was higher if a nephroscope rather than a ureteroscope was used (p = 0.045). CONCLUSIONS: Operation time was a risk factor for both septic shock and severe hemorrhage. The patients without hydronephrosis before operation were more likely to suffer severe renal bleeding. Reducing intraoperative puncture time can reduce the probability of severe post-PCNL hemorrhage. The use of a comparatively gross nephroscope passage was likely to result in severe renal bleeding.

Percutaneous nephrolithotomy for staghorn stones in patients with solitary kidney in prone position or in completely supine position: a single-center experience.

PURPOSE: To evaluate the effectivity and safety of percutaneous nephrolithotomy (PCNL) in the treatment of solitary kidney with staghorn stones in prone position or in completely supine position. MATERIALS AND METHODS: We retrospectively reviewed the records of 18 patients with staghorn stones in a solitary kidney treated with PCNL. 12 patients underwent PCNL in prone position (group A). 6 patients underwent PCNL in completely supine position (group B). Demographic data, number of accesses, operating time, stone free rate, hemoglobin values, hospital stay and complications were studied. Serum creatinine, systolic and diastolic blood pressure, and new onset hypertension were determined preoperatively and postoperatively at 3 months. RESULTS: No blood transfusions were required and no abdominal or thoracic organ injuries were reported in both groups. The mean operative time was 104 minutes (range: 72-145 minutes) and 128 minutes (range: 80-170 minutes), respectively. The I stage stone free rate was 91.7 % and 83.3 %, respectively. There was no new onset hypertension by the end of follow-up in both groups. Both groups showed a similar fall in serum creatinine at 3 month follow-up period (p = 0.004 and 0.029, respectively). Systolic blood pressure showed a statistically significant improvement in group B (p = 0.034). CONCLUSION: PCNL is safe and has an acceptably high stone free rate in patients with solitary kidneys in both prone and completely supine position. At short-term follow-up, systolic blood pressure had improved in PCNL in supine position.

Fe(III)-Doped Polyaminopyrrole Nanoparticle for Imaging-Guided Photothermal Therapy of Bladder Cancer.

Clinically, the surgical treatment of bladder cancer often faces the problem of tumor recurrence, and the surgical treatment combined with postoperative chemotherapy to inhibit tumor recurrence also faces high toxicity and side effects. Therefore, the need for innovative bladder cancer treatments is urgent. For the past few years, with the development of nano science and technology, imaging-guided therapy using nanomaterials with both imaging and therapy functions has shown great advantages and can not only identify the locations of the tumors but also exhibit biodistributions of nanomaterials in the tumors, significantly improving the accuracy and efficacy of treatment. In this work, we synthesized Fe(III)-doped polyaminopyrrole nanoparticles (FePPy-NH2 NPs). With low cytotoxicity and a blood circulation half-life of 7.59 h, high levels of FePPy-NH2 NPs accumulated in bladder tumors, with an accumulation rate of up to 5.07%ID/g. The coordination of Fe(III) and the amino group in the structure can be used for magnetic resonance imaging (MRI), whereas absorption in the near-infrared region can be applied to photoacoustic imaging (PAI) and photothermal therapy (PTT). MRI and PAI accurately identified the location of the tumor, and based on the imaging data, laser irradiation was employed accurately. With a high photothermal conversion efficiency of 44.3%, the bladder tumor was completely resected without recurrence. Hematological analysis and histopathological analysis jointly confirmed the high level of safety of the experiment.

Efficacy of compound aluminum sulfate injection as a monotherapeutic regimen in non-muscle invasive bladder cancer patients: a retrospective single-arm cohort study.

Background: Compound aluminum sulfate injection (CASI) originated from a Chinese traditional medicine, "Kuzhiye", and has been used in treating non-muscle invasive bladder cancer (NMIBC). Previous studies suggested that CASI was a potential monotherapeutic drug for NMIBC. However, the efficacy and safety of CASI in the treatment of NMIBC, as well as the long-term recurrence after treatment, need to be further evaluated. Methods: A multicenter retrospective single-arm cohort study was conducted. From 2006 to 2009, 101 patients (74 men and 27 women, aged 58.9±11.9 years) with T1 or benign NMIBC were enrolled. Each patient was directly injected with CASI through catheter needle into the root of NMIBC. Vital signs, electrocardiography, blood count, blood biochemistry, and urine analysis were re-examined on day 2 and day 14 after CASI injection, together with a cystoscopic examination 4 weeks after CASI treatment was performed for all patients to assess the clinical activity and safety of CASI. To study long-term efficacy, patients in center 2 were followed up for recurrence with a median follow-up time of 13.8 years. Results: For the 101 patients enrolled in this study, demographic characteristics in the 3 centers showed no significant differences. After CASI, 2 patients showed administration site-dependent, but not dose-dependent, increase in their aluminum concentration in 24 hours without obvious abnormality in blood biochemistry. The overall effective rate was 97.03%, including complete tumor necrosis in 94 patients. Treatment-related adverse events occurred in 20 patients (19.80%), including 9 drug-related and 11 cystoscopy-related adverse events (AEs). All AEs were endurable and disappeared within 2 weeks without any treatment. The maximum tolerated single dose of CASI was 21 mL. Among the 43 patients at center 2, 3 patients were excluded because they changed to other treatment regimen. As of April 2022, of the 40 patients enrolled, 22 had no recurrence and 7 relapsed. The follow-up time was 2-16.2 years. The other 11 patients were lost to follow up. Conclusions: CASI may be an effective and safe option for the treatment of NMIBC and is expected to be a potential monotherapy regimen for NMIBC.

Functional Nanomedicines for Targeted Therapy of Bladder Cancer.

Bladder cancer is one of most common malignant urinary tract tumor types with high incidence worldwide. In general, transurethral resection of non-muscle-invasive bladder cancer followed by intravesical instillation of chemotherapy is the standard treatment approach to minimize recurrence and delay progression of bladder cancer. However, conventional intravesical chemotherapy lacks selectivity for tumor tissues and the concentration of drug is reduced with the excretion of urine, leading to frequent administration and heavy local irritation symptoms. While nanomedicines can overcome all the above shortcomings and adhere to the surface of bladder tumors for a long time, and continuously and efficiently release drugs to bladder cancers. The rapid advances in targeted therapy have led to significant improvements in drug efficacy and precision of targeted drug delivery to eradicate tumor cells, with reduced side-effects. This review summarizes the different available nano-systems of targeted drug delivery to bladder cancer tissues. The challenges and prospects of targeted therapy for bladder cancer are additionally discussed.

HAMLET treatment delays bladder cancer development.

PURPOSE: HAMLET is a protein-lipid complex that kills different types of cancer cells. Recently we observed a rapid reduction in human bladder cancer size after intravesical HAMLET treatment. In this study we evaluated the therapeutic effect of HAMLET in the mouse MB49 bladder carcinoma model. MATERIALS AND METHODS: Bladder tumors were established by intravesical injection of MB49 cells into poly L-lysine treated bladders of C57BL/6 mice. Treatment groups received repeat intravesical HAMLET instillations and controls received alpha-lactalbumin or phosphate buffer. Effects of HAMLET on tumor size and putative apoptotic effects were analyzed in bladder tissue sections. Whole body imaging was used to study HAMLET distribution in tumor bearing mice compared to healthy bladder tissue. RESULTS: HAMLET caused a dose dependent decrease in MB49 cell viability in vitro. Five intravesical HAMLET instillations significantly decreased tumor size and delayed development in vivo compared to controls. TUNEL staining revealed selective apoptotic effects in tumor areas but not in adjacent healthy bladder tissue. On in vivo imaging Alexa-HAMLET was retained for more than 24 hours in the bladder of tumor bearing mice but not in tumor-free bladders or in tumor bearing mice that received Alexa-alpha-lactalbumin. CONCLUSIONS: Results show that HAMLET is active as a tumoricidal agent and suggest that topical HAMLET administration may delay bladder cancer development.

Preparation and Characterization of Chitosan Nanoparticles for Chemotherapy of Melanoma Through Enhancing Tumor Penetration.

The poor solubility and permeability of most chemotherapeutic drugs lead to unsatisfactory bioavailability combined with insufficient drug concentration. In this study, positively charged nanoparticles based on chitosan were developed and synthesized to enhance tumor penetration capability of 10-Hydroxycamptothecin (HCPT) in order to improve the chemotherapeutic effect of melanoma. The HCPT encapsulated nanoparticles were noted as NPs/HCPT. NPs/HCPT was characterized by dynamic light scattering and zeta potential measurements. In addition, cell uptake, in vitro cytotoxicity, apoptosis and in vivo antitumor activity of NPs/HCPT were further investigated. The average diameter of NPs/HCPT was approximately 114.6 ± 4.1 nm. The viability of murine melanoma cell lines (B16F10 and B16F1) was significantly decreased due to interaction with NPs/HCPT. Moreover, NPs/HCPT significantly inhibited the progression of tumors. These investigations implied that cationic NPs/HCPT could be potentially applied as a promising drug delivery nanosystem.

Intravesical Hydrogels as Drug Reservoirs.

The complex environment in the bladder weakens the efficacy of intravesical therapy. Hydrogel-based drug delivery systems are poised to revolutionize the delivery of therapeutic agents to bladder lesion sites. This forum article highlights the prospective applications of hydrogels as drug reservoirs in treating chronic bladder diseases.

Synergistically Enhanced Mucoadhesive and Penetrable Polypeptide Nanogel for Efficient Drug Delivery to Orthotopic Bladder Cancer.

Intravesical chemotherapy has been recommended after the gold standard of transurethral resection of the bladder tumor to prevent bladder cancer (BC) from local recurrence in the clinic. However, due to rapid urine excretion and barrier protection of the bladder wall, the clinical performances of chemotherapeutic drugs are severely compromised. In the present work, a smart positively charged disulfide-crosslinked nanogel of oligoarginine-poly(ethylene glycol)-poly(L-phenylalanine-co-L-cystine) (R9-PEG-P(LP-co-LC)) was prepared to prolong the retention period and enhance the penetration capability of chemotherapeutic agent toward the bladder wall. PEG significantly improved the aqueous dispersibility of the 10-hydroxycamptothecin (HCPT)-loaded R9-PEG-P(LP-co-LC) (i.e., R9NG/HCPT) and enhanced the mucoadhesive capability by the nonspecific interaction between PEG chain and the bladder mucosa accompanied with the electrostatic interaction between the cationic R9 and negatively charged bladder mucosa. Besides, R9, as a cell-penetrating peptide, efficiently penetrated through the cell membrane and delivered carried cargo. The disulfide bond endowed the selective release behavior of HCPT triggered by the intracellular reductive microenvironment. As an advanced chemotherapeutic nanoformulation, the smart R9NG/HCPT demonstrated superior cytotoxicity against human BC 5637 cells in vitro and remarkably enhanced tumor suppression activity toward orthotopic BC models of mouse and rat in vivo, indicating its great potential in the clinical intravesical BC chemotherapy.