Electrospun nanofibrous scaffolds as a platform to reduce melanoma tumour growth, recurrence, and promote post-resection wound repair.

Wound healing following skin tumour surgery still remains a major challenge. To address this issue, polysaccharide-loaded nanofibrous mats have been engineered as skin patches on the wound site to improve wound healing while simultaneously eliminating residual cancer cells which may cause cancer relapse. The marine derived polysaccharides kappa-carrageenan (KCG) and fucoidan (FUC) were blended with polydioxanone (PDX) nanofibers due to their inherent anti-cancer activity conferred by the sulphate groups as well as their immunomodulatory properties which can reduce inflammation resulting in accelerated wound healing. KCG and FUC were released sustainably from the blend nanofibers via the Korsmeyer-Peppas kinetics. MTT assays, live/dead staining and SEM images demonstrated the toxicity of KCG and FUC towards skin cancer MP 41 cells. In addition, MP 41 cells showed reduced metastatic potential when grown on KCG or FUC containing mats. Both KCG and FUC were non- cytotoxic to healthy L 929 fibroblast cells. In vivo studies on healthy Wistar rats confirmed the non-toxicity of the nanofibrous patches as well as their improved and scarless wound healing potential. In vivo studies on tumour xenograft model further showed a reduction of 7.15 % in tumour volume in only 4 days following application of the transdermal patch.

Short Antiangiogenic MMP-2 Peptide-Decorated Conjugated Linoleic Acid-Coated SPIONs for Targeted Paclitaxel Delivery in an A549 Cell Xenograft Mouse Tumor Model.

The design of targeted antiangiogenic nanovectors for the delivery of anticancer drugs presents a viable approach for effective management of nonsmall-cell lung carcinoma (NSCLC). Herein, we report on the fabrication of a targeted delivery nanosystem for paclitaxel (PTX) functionalized with a short antimatrix metalloproteinase 2 (MMP-2) CTT peptide for selective MMP-2 targeting and effective antitumor activity in NSCLC. The fabrication of the targeted nanosystem (CLA-coated PTX-SPIONs@CTT) involved coating of superparamagnetic iron-oxide nanoparticles (SPIONs) with conjugated linoleic acid (CLA) via chemisorption, onto which PTX was adsorbed, and subsequent surface functionalization with carboxylic acid groups for conjugation of the CTT peptide. CLA-coated PTX SPIONs@CTT had a mean particle size of 99.4 nm and a PTX loading efficiency of ∼98.5%. The nanosystem exhibited a site-specific in vitro PTX release and a marked antiproliferative action on lung adenocarcinoma cells. The CTT-functionalized nanosystem significantly inhibited MMP-2 secretion by almost 70% from endothelial cells, indicating specific anti-MMP-2 activity. Treatment of tumor-bearing mice with subcutaneous injection of the CTT-functionalized nanosystem resulted in 69.7% tumor inhibition rate, and the administration of the nanosystem subcutaneously prolonged the half-life of PTX and circulation time in vivo. As such, CLA-coated PTX-SPIONs@CTT presents with potential for application as a targeted nanomedicine in NSCLC management.

Pre-Clinical Investigations of the Pharmacodynamics of Immunogenic Smart Radiotherapy Biomaterials (iSRB).

The use of an immunogenic smart radiotherapy biomaterial (iSRB) for the delivery of anti-CD40 is effective in treating different cancers in animal models. This study further characterizes the use of iSRBs to evaluate any associated toxicity in healthy C57BL6 mice. iSRBs were fabricated using a poly-lactic-co-glycolic-acid (PLGA) polymer mixed with titanium dioxide (TiO2) nanoparticles incorporated into its matrix. Animal studies included investigations of freely injected anti-CD40, anti-CD40-loaded iSRBs, unloaded iSRBs and control (healthy) animal cohorts. Mice were euthanized at pre-determined time points post-treatment to evaluate the serum chemistry pertaining to kidney and liver toxicity and cell blood count parameters, as well as pathology reports on organs of interest. Results showed comparable liver and kidney function in all cohorts. The results indicate that using iSRBs with or without anti-CD40 does not result in any significant toxicity compared to healthy untreated animals. The findings provide a useful reference for further studies aimed at optimizing the therapeutic efficacy and safety of iSRBs and further clinical translation work.

Patient reported outcomes following whole brain radiotherapy in patients with brain metastases in NSIA-LUTH Cancer Center.

BACKGROUND: Brain metastases (BM) are a common complication in advanced cancer patients, and extremely challenging to treat. Consequently, whole brain radiotherapy (WBRT) remains the standard palliative intervention for patients with BM. The present study set to evaluate the clinical benefits of WBRT by assessing the quality of life (QoL) in WBRT-treated patients with BM, in Nigeria. METHODS: This was a prospective, longitudinal, hospital-based single-centre study. Consecutive sampling methodology was used to recruit 52 patients with BM undergoing WBRT. Patients were followed up on days 7, 30, 90 and 180 after WBRT. The EORTC QLQ-C15-PAL and EORTC QLQ-BN20 were employed to report patients' responses. The likert scale responses were linearly converted into 0 - 100 scores, and the descriptive analysis was conducted using IBM SPSS Statistics 29.0, at 95% confidence interval, using the two-tailed t-test for continuous variables or the chi-square test for categorical values. The overall survival was calculated with the Kaplan Maier method and the difference tested with Log-rank method, considering the interval from the baseline until death or end of the study. RESULTS: The study cohort was predominantly females (82.7%), and accordingly, 65.4% of the respondents had a breast primary tumor. A goodness-of-fit test yielded non-significant Chi square Pearson (p = 0.325) and Deviance (p = 1.000) residuals, indicating the best fit. The median overall survival was 180 days (~ 6 months). A total of 20 patients (38%) that survived up to 180 days reported alleviated symptoms and better functioning. A significant improvement in physical functioning (p < 0.001) and emotional functioning (p = 0.031) was reported at 180 days post WBRT, compared to baseline. CONCLUSIONS: WBRT is an effective palliative intervention in patients with BM, resulting in improved QoL. More than 50% of patients that survived ~ 3 months reported alleviation of pain, and 38% of patients that survived for ~ 6 months reported a significantly improved functioning. This demonstrated the clinical benefits of WBRT in palliative care and will add to the body of data on the use of WBRT, from Africa.

Surface Immobilization of Anti-VEGF Peptide on SPIONs for Antiangiogenic and Targeted Delivery of Paclitaxel in Non-Small-Cell Lung Carcinoma.

A design has been established for the surface decoration of superparamagnetic iron oxide nanoparticles (SPIONs) with anti-vascular endothelial growth factor peptide, HRH, to formulate a targeted paclitaxel (PTX) delivery nanosystem with notable tumor targetability and antiangiogenic activity. The design methodology included (i) tandem surface functionalization via coupling reactions, (ii) pertinent physicochemical characterization, (iii) in vitro assessment of drug release, anti-proliferative activity, and quantification of vascular endothelial growth factor A (VEGF-A) levels, and (iv) in vivo testing using a lung tumor xenograft mouse model. Formulated CLA-coated PTX-SPIONs@HRH depicted a size and surface charge of 108.5 ± 3.5 nm and -30.4 ± 2.3 mV, respectively, and a quasi-spherical shape relative to pristine SPIONs. Fourier transform infrared (FTIR) analysis and estimation of free carboxylic groups supported the preparation of the CLA-coated PTX-SPIONs@HRH. CLA-coated PTX-SPIONs@HRH exhibited high PTX loading efficiency (98.5%) and sustained release in vitro, with a marked dose dependent anti-proliferative activity in A549 lung adenocarcinoma cells, complimented by an enhanced cellular uptake. CLA-coated PTX-SPIONs@HRH significantly reduced secretion levels of VEGF-A in human dermal microvascular endothelial cells from 46.9 to 35.6 pg/mL compared to untreated control. A 76.6% tumor regression was recorded in a lung tumor xenograft mouse model following intervention with CLA-coated PTX-SPIONs@HRH, demonstrating tumor targetability and angiogenesis inhibition. CLA-coated PTX-SPIONs@HRH enhanced the half-life of PTX by almost 2-folds and demonstrated a prolonged PTX plasma circulation time from a subcutaneous injection (SC). Thus, it is suggested that CLA-coated PTX-SPIONs@HRH could provide a potential effective treatment modality for non-small-cell lung carcinoma as a nanomedicine.

Recent Innovations and Nano-Delivery of Actinium-225: A Narrative Review.

The actinium-225 (225Ac) radioisotope exhibits highly attractive nuclear properties for application in radionuclide therapy. However, the 225Ac radionuclide presents multiple daughter nuclides in its decay chain, which can escape the targeted site, circulate in plasma, and cause toxicity in areas such as kidneys and renal tissues. Several ameliorative strategies have been devised to circumvent this issue, including nano-delivery. Alpha-emitting radionuclides and nanotechnology applications in nuclear medicine have culminated in major advancements that offer promising therapeutic possibilities for treating several cancers. Accordingly, the importance of nanomaterials in retaining the 225Ac daughters from recoiling into unintended organs has been established. This review expounds on the advancements of targeted radionuclide therapy (TRT) as an alternative anticancer treatment. It discusses the recent developments in the preclinical and clinical investigations on 225Ac as a prospective anticancer agent. Moreover, the rationale for using nanomaterials in improving the therapeutic efficacy of α-particles in targeted alpha therapy (TAT) with an emphasis on 225Ac is discussed. Quality control measures in the preparation of 225Ac-conjugates are also highlighted.

Synthesis of Novel Conjugated Linoleic Acid (CLA)-Coated Superparamagnetic Iron Oxide Nanoparticles (SPIONs) for the Delivery of Paclitaxel with Enhanced In Vitro Anti-Proliferative Activity on A549 Lung Cancer Cells.

The application of Superparamagnetic Iron Oxide Nanoparticles (SPIONs) as a nanomedicine for Non-Small Cell Lung Carcinoma (NSCLC) can provide effective delivery of anticancer drugs with minimal side-effects. SPIONs have the flexibility to be modified to achieve enhanced oading of hydrophobic anticancer drugs such as paclitaxel (PTX). The purpose of this study was to synthesize novel trans-10, cis-12 conjugated linoleic acid (CLA)-coated SPIONs loaded with PTX to enhance the anti-proliferative activity of PTX. CLA-coated PTX-SPIONs with a particle size and zeta potential of 96.5 ± 0.6 nm and -27.3 ± 1.9 mV, respectively, were synthesized. The superparamagnetism of the CLA-coated PTX-SPIONs was confirmed, with saturation magnetization of 60 emu/g and 29 Oe coercivity. CLA-coated PTX-SPIONs had a drug loading efficiency of 98.5% and demonstrated sustained site-specific in vitro release of PTX over 24 h (i.e., 94% at pH 6.8 mimicking the tumor microenvironment). Enhanced anti-proliferative activity was also observed with the CLA-coated PTX-SPIONs against a lung adenocarcinoma (A549) cell line after 72 h, with a recorded cell viability of 17.1%. The CLA-coated PTX-SPIONs demonstrated enhanced suppression of A549 cell proliferation compared to pristine PTX, thus suggesting potential application of the nanomedicine as an effective site-specific delivery system for enhanced therapeutic activity in NSCLC therapy.

A review on engineered magnetic nanoparticles in Non-Small-Cell lung carcinoma targeted therapy.

There are growing appeals forthe design of efficacious treatment options for non-small-cell lung carcinoma (NSCLC) as it accrues to ~ 85% cases of lung cancer. Although platinum-based doublet chemotherapy has been the main therapeutic intervention in NSCLC management, this leads to myriad of problems including intolerability to the doublet regimens and detrimental side effects due to high doses. A new approach is therefore needed and warrants the design of targeted drug delivery systems that can halt tumor proliferation and metastasis by targeting key molecules, while exhibiting minimal side effects and toxicity. This review aims to explore the rational design of magnetic nanoparticles for the development of tumor-targeting systems for NSCLC. In the review, we explore the anticancer merits of conjugated linoleic acid (CLA) and provide a concise incursion into its application for the invention of functionalized magnetic nanoparticles in the targeted treatment of NSCLC. Recent nanoparticle-based targeted chemotherapies for targeting angiogenesis biomarkers in NSCLC will also be reviewed to further highlight versatility of magnetic nanoparticles. These developments through molecular tuning at the nanoscale and supported by comprehensive pre-clinical studies could lead to the establishment of precise nanosystems for tumor-homing cancer therapy.