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Case 3 clinical photographs. A, Right leg in-transit metastatic melanoma lesions before application of topical imiquimod. B, Right leg lesions 6 months after imiquimod application.
Contexts in source publication
Context 1
... emission tomographyecomputed tomography and magnetic resonance imaging were negative for distant metastases. Five months later, the patient developed skin-colored papules surrounding the excision site consistent with in-transit metastases (BRAF wild type) (Fig 3, A). The lesions clinically resolved after biopsy, but within 1 month, new nodules developed that were deemed unresectable. ...
Context 2
... lesions clinically resolved after biopsy, but within 1 month, new nodules developed that were deemed unresectable. He was treated with cryotherapy followed by 3 months of topical imiquimod leading to complete resolution of the in-transit metastases (Fig 3, B). During treatment, flurodeoxyglucose-avidity was noted in the right external iliac region; however, all lymph nodes were too small to biopsy at that time and therefore he was monitored with imaging every 3 months. ...
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Background
Nano-Pulse Stimulation™ Therapy (NPS™) is a new, bioelectric modality that applies ultrashort pulses of electric energy to trigger regulated cell death in treated tissues. Instead of initiating necrosis by heating or freezing, NPS therapy permeabilizes intracellular organelles to activate the cell’s own self-destruct pathway of programme...
Citations
... In contrast, cell-based vaccination methods are often more costly and less consistent in terms of reproducibility when compared to the administration of a targeted nanoformulation injection for delivery to lymph nodes [15]. Imiquimod (IMQ) is a highly potent agent that modulates both the innate and adaptive immune responses [16]. Its mechanism of action involves mainly binding to toll-like receptors 7, which is present on antigen-presenting cells [17,18]. ...
... Its mechanism of action involves mainly binding to toll-like receptors 7, which is present on antigen-presenting cells [17,18]. By doing so, IMQ enhances the stimulation of T cells and promotes the activation of tumor-specific T-cell responses [16]. In addition to its immunostimulatory effects, IMQ has demonstrated anti-angiogenic and pro-apoptotic properties both in vitro and in vivo [19]. ...
Objective
This study aims to utilize PEGylated poly (lactic-co-glycolic acid) (PLGA) nanoparticles as a delivery system for simultaneous administration of the BRAFV600E peptide, a tumor-specific antigen, and imiquimod (IMQ). The objective is to stimulate dendritic cell (DC) maturation, activate macrophages, and facilitate antigen presentation in C57BL6 mice.
Methods
PEG-PLGA-IMQ-BRAFV600E nanoparticles were synthesized using a PLGA-PEG-PLGA tri-block copolymer, BRAFV600E, and IMQ. Characterization included size measurement and drug release profiling. Efficacy was assessed in inhibiting BPD6 melanoma cell growth and activating immature bone marrow DCs, T cells, macrophages, and splenocyte cells through MTT and ELISA assays. In vivo, therapeutic and immunogenic effects potential was evaluated, comparing it to IMQ + BRAFV600E and PLGA-IMQ-BRAFV600E nanoparticles in inhibiting subcutaneous BPD6 tumor growth.
Results
The results highlight the successful synthesis of PEG-PLGA-IMQ-BRAFV600E nanoparticles (203 ± 11.1 nm), releasing 73.4% and 63.2% of IMQ and BARFV600E, respectively, within the initial 48 h. In vitro, these nanoparticles demonstrated a 1.3-fold increase in potency against BPD6 cells, achieving ~ 2.8-fold enhanced cytotoxicity compared to PLGA-IMQ-BRAFV600E. Moreover, PEG-PLGA-IMQ-BRAFV600E exhibited a 1.3-fold increase in potency for enhancing IMQ cytotoxic effects and a 1.1- to ~ 2.4-fold increase in activating DCs, T cells, macrophages, and splenocyte cells compared to IMQ-BRAFV600E and PLGA-IMQ-BRAFV600E. In vivo, PEG-PLGA-IMQ-BRAFV600E displayed a 1.3- to 7.5-fold increase in potency for inhibiting subcutaneous BPD6 tumor growth compared to the other formulations.
Conclusions
The findings suggest that PEG-PLGA nanoparticles effectively promote DC maturation, T cell activation, and potentially macrophage activation. The study highlights the promising role of this nanocomposite in vaccine development.
