Successful Salvage Brachytherapy after Infusion of Gold AuroShell Nanoshells for Localized Prostate Cancer in a Human Patient
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ABSTRACT:
SUBMITTER: Sung D
PROVIDER: S-EPMC10111943 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Gold nanoshells have been actively applied in industries beyond the research stage because of their unique optical properties. Although numerous methods have been reported for gold nanoshell synthesis, the labor-intensive and time-consuming production process is an issue that must be overcome to meet industrial demands. To resolve this, we report a high-throughput synthesis method for nanogap-rich gold nanoshells based on a core silica support (denoted as SiO2@Au NS), affording a 50-fold increase in scale by combining it with a dual-channel infusion pump system. By continuously dropping the reactant solution through the pump, nanoshells with closely packed Au nanoparticles were prepared without interparticle aggregation. The thickness of the gold nanoshells was precisely controlled at 2.3-17.2 nm by regulating the volume of the reactant solution added dropwise. Depending on the shell thickness, the plasmonic characteristics of SiO2@Au NS prepared by the proposed method could be tuned. Moreover, SiO2@Au NS exhibited surface-enhanced Raman scattering activity comparable to that of gold nanoshells prepared by a previously reported low-throughput method at the same reactant ratio. The results indicate that the proposed high-throughput synthesis method involving the use of a dual-channel infusion system will contribute to improving the productivity of SiO2@Au NS with tunable plasmonic characteristics.
| S-EPMC10855030 | biostudies-literature
Project description:PurposeThe aim of this study is to determine if a repeated hydrogel injection in a previously irradiated patient prior to salvage high-dose-rate brachytherapy (HDR-BT) is feasible.Material and methodsA 61-year-old man with an organ confined (cT1c cN0 cM0, Gleason score 3 + 3 = 6, initial prostate-specific antigen [PSA] 7.9 ng/ml) prostate cancer was previously treated with HDR-BT (3 fractions of 11.5 Gy every 2nd week) after hydrogel injection to reduce the rectal dose. Ten months after, an isolated local persistence was seen on a PSMA PET-CT. Nadir PSA was 2.0 ng/ml, 3 months after treatment and was 3.95 ng/ml by the re-treatment. Salvage therapy consisted of HDR-BT (3 fractions of 9 Gy every 2nd week) with a simultaneous integrated boost to the residual region. Again, a hydrogel injection (10 ml) was applied to reduce the rectal dose prior to the treatment.ResultsBoth hydrogel injection and salvage HDR-BT could be applied without any significant complications or toxicity. A good PSA response was observed with a nadir of 0.42 ng/ml, twelve months after salvage therapy. Acute toxicity (max grade II) resolved within 2 days after treatment.ConclusionsThe use of a hydrogel prior to salvage HDR-BT in a patient previously treated with HDR-BT is feasible and could help reduce the rectal exposure in the salvage setting.
| S-EPMC5961532 | biostudies-literature
Project description:IntroductionTreatment strategy for castration-resistant prostate cancer with neuroendocrine differentiation after radiation therapy has not been established.Case presentationWe described a case of castration-resistant prostate cancer with neuroendocrine differentiation after initial external beam radiotherapy followed by salvage androgen deprivation therapy. Magnetic resonance imaging detected recurrence of a suspicious lesion in the left lobe of the prostate, although the prostate-specific antigen level was <0.2 ng/mL. Transperineal prostate saturation needle biopsy detected adenocarcinoma with neuroendocrine differentiation. The patient underwent salvage focal brachytherapy and had a prostate-specific antigen progression-free survival of 20 months with no obvious adverse events. No recurrence has been detected on magnetic resonance imaging for 18 months.ConclusionSalvage focal brachytherapy for prostate cancer after external beam radiotherapy can be one of the treatment strategies for local recurrence of castration-resistant prostate cancer with neuroendocrine differentiation.
| S-EPMC9249630 | biostudies-literature
Project description:Prostate cancer is the most prevalent cancer amongst men. For localized disease, there currently exist several reliable treatment modalities including surgery, radiotherapy and brachytherapy. Our growing understanding of this disease indicates that local control plays a very important role in prevention of subsequent dissemination. Many improvements to external beam radiotherapy over recent years have decreased toxicity and improved outcomes, but nonetheless, local relapse remains common. Many salvage options exist for locally recurrent prostate cancer, but are rarely offered, partly because of the fear of toxicity. Many men with isolated local recurrence therefore do not receive potentially curative second line treatment and are instead treated with palliative androgen suppression. Selection plays an important role in determining which individuals are likely to benefit from salvage. Those at high risk of pre-existing micro-metastatic disease despite negative staging scans are unlikely to benefit. Prostate brachytherapy has evolved over the more than 3 decades of experience. Modern techniques allow more precise tumor localization and dose delivery. Better understanding of dosimetric parameters can distinguish optimal from suboptimal implants. Salvage brachytherapy can be an effective treatment for locally recurrent prostate cancer after prior external beam radiotherapy. We review the literature pertaining to both low dose rate (LDR) and high dose rate (HDR) salvage brachytherapy and discuss patient selection, optimal dose, treatment volume and toxicity avoidance.
| S-EPMC6043745 | biostudies-literature
Project description:PurposeNCT03253744 is a phase 1 trial with the primary objective to identify the maximum tolerated dose (MTD) of salvage stereotactic body radiation therapy (SBRT) in patients with local prostate cancer recurrence after brachytherapy. Additional objectives included biochemical control and imaging response.Methods and materialsThis trial was initially designed to test 3 therapeutic dose levels (DLs): 40 Gy (DL1), 42.5 Gy (DL2), and 45 Gy (DL3) in 5 fractions. Intensity modulation was used to deliver the prescription dose to the magnetic resonance imaging and prostate-specific membrane antigen-based positron emission tomography imaging-defined gross tumor volume while simultaneously delivering 30 Gy to an elective volume defined by the prostate gland. This phase 1 trial followed a 3+3 design with a 3-patient expansion at the MTD. Toxicities were scored until trial completion at 2 years post-SBRT using Common Terminology Criteria for Adverse Events version 5.0. Escalation was halted if 2 dose limiting toxicities occurred, defined as any persistent (>4 days) grade 3 toxicity occurring within the first 3 weeks after SBRT or any grade ≥3 genitourinary (GU) or grade 4 gastrointestinal toxicity thereafter.ResultsBetween August 2018 and January 2023, 9 patients underwent salvage SBRT and were observed for a median of 22 months (Q1-Q3, 20-43 months). No grade 3 to 5 adverse events related to study treatment were observed; thus, no dose limiting toxicities occurred during the observation period. Escalation was halted by amendment given excellent biochemical control in DL1 and DL2 in the setting of a high incidence of clinically significant late grade 2 GU toxicity. Therefore, the MTD was considered 42.5 Gy in 5 fractions (DL2). One- and 2-year biochemical progression-free survival were 100% and 86%, representing a single patient in the trial cohort with biochemical failure (prostate-specific antigen [PSA] nadir + 2.0) at 20 months posttreatment.ConclusionsThe MTD of salvage SBRT for the treatment of intraprostatic radiorecurrence after brachytherapy was 42.5 Gy in 5 fractions producing an 86% 2-year biochemical progression-free survival rate, with 1 poststudy failure at 20 months. The most frequent clinically significant toxicity was late grade 2 GU toxicity.
| S-EPMC11262986 | biostudies-literature
Project description:The dependence of the localized surface plasmon resonance (LSPR) of noble-metal nanomaterials on refractive index makes LSPR a useful, label-free signal transduction strategy for biosensing. In particular, by decorating gold nanomaterials with molecular recognition agents, analytes of interest can be trapped near the surface, resulting in an increased refractive index surrounding the nanomaterial, and, consequently, a red shift in the LSPR wavelength. Ionic poly( N-isopropylacrylamide- co-methacrylic acid) (PNM) hydrogels were used as protein receptors because PNM nanogels exhibit a large increase in refractive index upon protein binding. Specifically, PNM hydrogels were synthesized on the surface of silica gold nanoshells (AuNSs). This composite material (AuNS@PNM) was used to detect changes in the concentration of two protein biomarkers of chronic dry eye: lysozyme and lactoferrin. Both of these proteins have high isoelectric points, resulting in electrostatic attraction between the negatively charged PNM hydrogels and positively charged proteins. Upon binding lysozyme or lactoferrin, AuNS@PNM exhibits large, concentration-dependent red shifts in LSPR wavelength, which enabled the detection of clinically relevant concentration changes of both biomarkers in human tears. The LSPR-based biosensor described herein has potential utility as an affordable screening tool for chronic dry eye and associated conditions.
| S-EPMC6156935 | biostudies-literature
Project description:Background and objectiveToxicity from local salvage therapy for radiorecurrent prostate cancer (PCa) remains a concern. This phase 2 study evaluates the outcomes of salvage magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (sTULSA).MethodsMen with biochemically relapsed, biopsy-proven PCa following definitive radiotherapy underwent whole- or partial-gland sTULSA (NCT03350529). Prostate-confined recurrence was confirmed by MRI and prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computed tomography (CT). The primary endpoints were safety (Clavien-Dindo classification) and efficacy (prostate-specific antigen [PSA], PSMA PET-CT, and MRI-targeted biopsy at 12 mo). The secondary endpoints included functional and survival outcomes.Key findings and limitationsThirty-nine patients underwent sTULSA (64% whole gland), with a median age of 73 yr (interquartile range [IQR]: 69-77) and PSA of 3.3 ng/ml (IQR: 2-6.2). Three patients had undergone prior salvage therapy, 16 were receiving hormonal therapy at enrollment, and 12 had a history of transurethral interventions. Eighteen patients had incidental urethral strictures on baseline cystoscopy. Over a median follow-up of 40 mo (IQR: 24-55), 56% experienced adverse events. Severe genitourinary toxicity (Clavien-Dindo ≥3 or hospitalization) occurred in 28%, including three patients with puboprostatic fistulas and two patients requiring cystectomy. Leak-free continence was maintained in 53%. At 12 mo, 89% showed no cancer in the targeted area, with a median PSA reduction of 95% (p < 0.001). Five-year metastasis-free, failure-free, and biochemical recurrence-free survival probabilities (95% confidence interval) were 97% (0.93-1.00), 70% (0.54-0.91), and 54% (0.31-0.93), respectively. Limitations included single-arm design and moderate sample size.Conclusions and clinical implicationsIt has been observed that sTULSA is effective for radiorecurrent PCa, although genitourinary toxicity remains a concern. Further studies should refine patient selection and treatment parameters to improve safety and tolerability.Patient summaryIn this study, we examined a new treatment called magnetic resonance imaging-guided transurethral ultrasound ablation for prostate cancer that has returned after radiation therapy. We found that the treatment provided effective and lasting cancer control for most patients. However, a notable number of patients experienced significant genitourinary toxicity, including severe adverse effects affecting urinary function. Careful patient selection is crucial to minimize these adverse effects and ensure the best results.
| S-EPMC11656090 | biostudies-literature
Project description:Targeted killing of cancer cells by engineered nanoparticles holds great promise for noninvasive photothermal therapy applications. We present the design and generation of a novel class of gold nanoshells with cores composed of self-assembled block copolypeptide vesicles with photothermal properties. Specifically, poly(L-lysine)60- block-poly(L-leucine)20 (K60L20) block copolypeptide vesicles coated with a thin layer of gold demonstrate enhanced absorption of light due to surface plasmon resonance (SPR) in the near-infrared range. We show that the polypeptide-based K60L20 gold nanoshells have low toxicity in the absence of laser exposure, significant heat generation upon exposure to near-infrared light, and, as a result, localized cytotoxicity within the region of laser irradiation in vitro. To gain a better understanding of our gold nanoshells in the context of photothermal therapy, we developed a comprehensive mathematical model for heat transfer and experimentally validated this model by predicting the temperature as a function of time and position in our experimental setup. This model can be used to predict which parameters of our gold nanoshells can be manipulated to improve heat generation for tumor destruction. To our knowledge, our results represent the first ever use of block copolypeptide vesicles as the core material of gold nanoshells.
| S-EPMC6070380 | biostudies-literature
Project description:PurposeTo compare health-related quality of life (HRQOL) of high-dose-rate brachytherapy (HDRB) versus low dose-rate brachytherapy (LDRB) for localized prostate cancer in a multi-institutional phase 2 randomized trial.Methods and materialsMen with favorable-risk prostate cancer were randomized between monotherapy brachytherapy with either Iodine-125 LDRB to 144 Gy or single-fraction Iridium-192 HDRB to 19 Gy. HRQOL and urinary toxicity were recorded at baseline and at 1, 3, 6, and 12 months using the Expanded Prostate Cancer Index Composite (EPIC)-26 scoring and the International Prostate Symptom Score (IPSS). Independent samples t test and mixed effects modeling were performed for continuous variables. Time to IPSS resolution, defined as return to its baseline score ±5 points, was calculated using Kaplan-Meier estimator curves with the log-rank test. A multiple-comparison adjusted P value of ≤.05 was considered significant.ResultsLDRB and HDRB were performed in 15 and 16 patients, respectively, for a total of 31 patients. At 3 months, patients treated with LDRB had a higher IPSS score (mean, 15.5 vs 6.0, respectively; P = .003) and lower EPIC urinary irritative score (mean, 69.2 vs 85.3, respectively; P = .037) compared with those who received HDRB. On repeated measures at 1, 3, 6, and 12 months, the IPSS (P = .003) and EPIC urinary irritative scores (P = .019) were significantly better in the HDR arm, translating into a lower urinary toxicity profile. There were no significant differences in the EPIC urinary incontinence, sexual, or bowel habit scores between the 2 groups at any measured time point. Time to IPSS resolution was significantly shorter in the HDRB group (mean, 2.0 months) compared with the LDRB group (mean, 6.0 months; P = .028).ConclusionsHDRB monotherapy is a promising modality associated with a lower urinary toxicity profile and higher HRQOL in the first 12 months compared with LDRB.
| S-EPMC6817536 | biostudies-literature
Project description:Currently, there is no curative treatment for advanced metastatic prostate cancer, and options, such as chemotherapy, are often nonspecific, harming healthy cells and resulting in severe side effects. Attaching targeting ligands to agents used in anticancer therapies has been shown to improve efficacy and reduce nonspecific toxicity. Furthermore, the use of triggered therapies can enable spatial and temporal control over the treatment. Here, we combined an engineered prostate cancer-specific targeting ligand, the A11 minibody, with a novel photothermal therapy agent, polypeptide-based gold nanoshells, which generate heat in response to near-infrared light. We show that the A11 minibody strongly binds to the prostate stem cell antigen that is overexpressed on the surface of metastatic prostate cancer cells. Compared to nonconjugated gold nanoshells, our A11 minibody-conjugated gold nanoshell exhibited significant laser-induced, localized killing of prostate cancer cells in vitro. In addition, we improved upon a comprehensive heat transfer mathematical model that was previously developed by our laboratory. By relaxing some of the assumptions of our earlier model, we were able to generate more accurate predictions for this particular study. Our experimental and theoretical results demonstrate the potential of our novel minibody-conjugated gold nanoshells for metastatic prostate cancer therapy.
| S-EPMC6071911 | biostudies-literature