Liposome-based diagnostic and therapeutic applications for pancreatic cancer.

Pancreatic cancer is one of the harshest and most challenging cancers to treat, often labeled as incurable. Chemotherapy continues to be the most popular treatment yet yields a very poor prognosis. The main barriers such as inefficient drug penetration and drug resistance, have led to the development of drug carrier systems. The benefits, ease of fabrication and modification of liposomes render them as ideal future drug delivery systems. This review delves into the versatility of liposomes to achieve various mechanisms of treatment for pancreatic cancer. Not only are there benefits of loading chemotherapy drugs and targeting agents onto liposomes, as well as mRNA combined therapy, but liposomes have also been exploited for immunotherapy and can be programmed to respond to photothermal therapy. Multifunctional liposomal formulations have demonstrated significant pre-clinical success. Functionalising drug-encapsulated liposomes has resulted in triggered drug release, specific targeting, and remodeling of the tumor environment. Suppressing tumor progression has been achieved, due to their ability to more efficiently and precisely deliver chemotherapy. Currently, no multifunctional surface-modified liposomes are clinically approved for pancreatic cancer thus we aim to shed light on the trials and tribulations and progress so far, with the hope for liposomal therapy in the future and improved patient outcomes. STATEMENT OF SIGNIFICANCE: Considering that conventional treatments for pancreatic cancer are highly associated with sub-optimal performance and systemic toxicity, the development of novel therapeutic strategies holds outmost relevance for pancreatic cancer management. Liposomes are being increasingly considered as promising nanocarriers for providing not only an early diagnosis but also effective, highly specific, and safer treatment, improving overall patient outcome. This manuscript is the first in the last 10 years that revises the advances in the application of liposome-based formulations in bioimaging, chemotherapy, phototherapy, immunotherapy, combination therapies, and emergent therapies for pancreatic cancer management. Prospective insights are provided regarding several advantages resulting from the use of liposome technology in precision strategies, fostering new ideas for next-generation diagnosis and targeted therapies of pancreatic cancer.

Nanoparticle-mediated magnetic hyperthermia is an effective method for killing the human-infective protozoan parasite Leishmania mexicana in vitro.

Cutaneous leishmaniasis is a neglected tropical disease characterized by disfiguring skin lesions. Current chemotherapeutic options depend on toxic, expensive drugs that are both difficult to administer and becoming less effective due to increasing levels of resistance. In comparison, thermotherapy displays greater patient compliance and less adverse systemic effects, but there are still significant issues associated with this. The procedure is painful, requiring local anaesthetic, and is less effective against large lesions. Using nanoparticles to controllably generate heat in a localized manner may provide an alternative solution. Here we evaluate magnetic hyperthermia, using iron oxide magnetic nanoparticles, as a localized, heat-based method to kill the human-infective parasite in vitro. We assessed the effectiveness of this method against the differentiated, amastigote form of the parasite using three distinct viability assays: PrestoBlue, Live/Dead stain and a novel luciferase-based assay. Changes in amastigote morphology and ultrastructure were assessed by immunofluorescence, scanning and transmission electron microscopy. Our findings show that magnetic hyperthermia is an effective method to kill host-infective amastigotes, with morphological changes consistent with heat treatment. This method has the potential to be a step-change for research into new therapeutic options that moves away from the expensive chemotherapeutics currently dominating the research climate.

Hybrid gold-iron oxide nanoparticles as a multifunctional platform for biomedical application.

BACKGROUND: Iron oxide nanoparticles (IONPs) have increasing applications in biomedicine, however fears over long term stability of polymer coated particles have arisen. Gold coating IONPs results in particles of increased stability and robustness. The unique properties of both the iron oxide (magnetic) and gold (surface plasmon resonance) result in a multimodal platform for use as MRI contrast agents and as a nano-heater. RESULTS: Here we synthesize IONPs of core diameter 30 nm and gold coat using the seeding method with a poly(ethylenimine) intermediate layer. The final particles were coated in poly(ethylene glycol) to ensure biocompatibility and increase retention times in vivo. The particle coating was monitored using FTIR, PCS, UV-vis absorption, TEM, and EDX. The particles appeared to have little cytotoxic effect when incubated with A375M cells. The resultant hybrid nanoparticles (HNPs) possessed a maximal absorbance at 600 nm. After laser irradiation in agar phantom a ΔT of 32°C was achieved after only 90 s exposure (50 µg mL-1). The HNPs appeared to decrease T2 values in line with previously clinically used MRI contrast agent Feridex(®). CONCLUSIONS: The data highlights the potential of these HNPs as dual function MRI contrast agents and nano-heaters for therapies such as cellular hyperthermia or thermo-responsive drug delivery.