Investigating the Use of a Liquid Immunogenic Fiducial Eluter Biomaterial in Cervical Cancer Treatment.

Globally, cervical cancer is the fourth leading cancer among women and is dominant in resource-poor settings in its occurrence and mortality. This study focuses on developing liquid immunogenic fiducial eluter (LIFE) Biomaterial with components that include biodegradable polymers, nanoparticles, and an immunoadjuvant. LIFE Biomaterial is designed to provide image guidance during radiotherapy similar to clinically used liquid fiducials while enhancing therapeutic efficacy for advanced cervical cancer. C57BL6 mice were used to grow subcutaneous tumors on bilateral flanks. The tumor on one flank was then treated using LIFE Biomaterial prepared with the immunoadjuvant anti-CD40, with/without radiotherapy at 6 Gy. Computed tomography (CT) and magnetic resonance (MR) imaging visibility were also evaluated in human cadavers. A pharmacodynamics study was also conducted to assess the safety of LIFE Biomaterial in healthy C57BL6 female mice. Results showed that LIFE Biomaterial could provide both CT and MR imaging contrast over time. Inhibition in tumor growth and prolonged significant survival (* p < 0.05) were consistently observed for groups treated with the combination of radiotherapy and LIFE Biomaterial, highlighting the potential for this strategy. Minimal toxicity was observed for healthy mice treated with LIFE Biomaterial with/without anti-CD40 in comparison to non-treated cohorts. The results demonstrate promise for the further development and clinical translation of this approach to enhance the survival and quality of life of patients with advanced cervical cancer.

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.

Polydopamine Nanomaterials for Overcoming Current Challenges in Cancer Treatment.

In efforts to overcome current challenges in cancer treatment, multifunctional nanoparticles are attracting growing interest, including nanoparticles made with polydopamine (PDA). PDA is a nature-inspired polymer with a dark brown color. It has excellent biocompatibility and is biodegradable, offering a range of extraordinary inherent advantages. These include excellent drug loading capability, photothermal conversion efficiency, and adhesive properties. Though the mechanism of dopamine polymerization remains unclear, PDA has demonstrated exceptional flexibility in engineering desired morphology and size, easy and straightforward functionalization, etc. Moreover, it offers enormous potential for designing multifunctional nanomaterials for innovative approaches in cancer treatment. The aim of this work is to review studies on PDA, where the potential to develop multifunctional nanomaterials with applications in photothermal therapy has been demonstrated. Future prospects of PDA for developing applications in enhancing radiotherapy and/or immunotherapy, including for image-guided drug delivery to boost therapeutic efficacy and minimal side effects, are presented.

Mesoporous, anisotropic nanostructures from bioinspired polymeric catecholamine neurotransmitters and their potential application as photoacoustic imaging agents.

Mesoporous polydopamine (PDA) nanobowls, which can be prepared using Pluronic® F-127, ammonia, and 1,3,5-trimethylbenzene (TMB), are one of the most studied anisotropic nanoparticle systems. However, only limited reports on polymerised analogues polynorepinephrine (PNE) and polyepinephrine (PEP) exist. Herein, we present modifications to a one-pot, soft template method, originally applied to make PDA nanobowls, to fabricate new shape-anisotropic nanoparticles (mesoporous nanospheres or "nano-golf balls" and nanobowls) using PNE and PEP for the first time. These modifications include the use of different oil phases (TMB, toluene and o-xylene) and ammonia concentrations to induce anisotropic growth of PDA, PNE, and PEP particles. Moreover, this work features the application of oddly shaped PDA, PNE, and PEP nanoparticles as intravascular photoacoustic imaging enhancers in Intralipid®-India ink-based tissue-mimicking phantoms. Photoacoustic imaging experiments showed that mesoporous nanobowls exhibit stronger enhancement, in comparison to their mesoporous nano-golf ball and nanoaggregate counterparts. The photoacoustic enhancement also followed the general trend PDA > PNE > PEP due to the differences in the rates of polymerisation of the monomers and the optical absorption of the resulting polymers. Lastly, about two- to four-fold enhancement in photoacoustic signals was observed for the mesoporous nanostructures, when compared to smooth nanospheres and their nano-aggregates. These results suggest that shape manipulation can aid in overcoming the inherently lower performance of PNE and PEP as photoacoustic imaging agents, compared to PDA. Since nanomaterials with mesoporous and anisotropic morphologies have significant, unexplored potential with emerging applications, these results set the groundwork for future studies on photoacoustically active oddly shaped PNE- and PEP-based nanosystems.

Synthesis and characterisation of polynorepinephrine-shelled microcapsules via an oil-in-water emulsion templating route.

In this article, we present a facile and robust method for the surfactant-free preparation of polynorepinephrine stabilised microcapsules templated from an oil-in-water emulsion. The resulting microcapsule structures are dependent on the concentration of Cu2+ used to catalyse norepinephrine polymerisation. When the concentration of Cu2+ increases, the diameter of the microcapsules and the thickness of the shell increase correspondingly. The mechanical and chemical stability provided by the polynorepinephrine shell are explored using surface pressure measurements and atomic force microscopy, demonstrating that a rigid and robust polynorepinephrine shell is formed. In order to demonstrate potential application of the microcapsules in sustained release, Nile red stained squalane was encapsulated, and pH responsive release was monitored. It was seen that by controlling pH, the release profile could be controlled, with highest release efficacy achieved in alkaline conditions, offering a new pathway for development of encapsulation systems for the delivery of water insoluble actives.

Photothermally responsive Pickering emulsions stabilised by polydopamine nanobowls.

Pickering emulsions with stimuli responsive properties have attracted mounting research attention owing to their potential for on-demand destabilisation of emulsions. However, a combination of biocompatibility and long-term stability are essential to efficiently apply such systems in biomedical applications, and this remains a significant challenge. To address current limitations, here we report the formation of photothermally responsive oil-in-water (o/w) Pickering emulsions fabricated using biocompatible stabilisers and showing prolonged stability. For the first time, we explore polydopamine (PDA) bowl-shaped mesoporous nanoparticles (PDA nanobowls) as a Pickering stabiliser without any surface modification or other stabiliser present. As-prepared PDA nanobowl-stabilised Pickering emulsions are shown to be pH responsive, and more significantly show high photothermal efficiency under near-infrared illumination due the incorporation of PDA into the system, which has remarkable photothermal response. These biocompatible, photothermally responsive o/w Pickering emulsion systems show potential in controlled drug release applications stimulated by NIR illumination.