A Biodegradable "One-For-All" Nanoparticle for Multimodality Imaging and Enhanced Photothermal Treatment of Breast Cancer.

Silver sulfide nanoparticles (Ag2S-NP) hold promise for various optical-based biomedical applications, such as near-infrared fluorescence (NIRF) imaging, photoacoustics (PA), and photothermal therapy (PTT). However, their NIR absorbance is relatively low, and previous formulations are synthesized using toxic precursors under harsh conditions and are not effectively cleared due to their large size. Herein, sub-5 nm Ag2S-NP are synthesized and encapsulated in biodegradable, polymeric nanoparticles (AgPCPP). All syntheses are conducted using biocompatible, aqueous reagents under ambient conditions. The encapsulation of Ag2S-NP in polymeric nanospheres greatly increases their NIR absorbance, resulting in enhanced optical imaging and PTT effects. AgPCPP nanoparticles exhibit potent contrast properties suitable for PA and NIRF imaging, as well as for computed tomography (CT). Furthermore, AgPCPP nanoparticles readily improve the conspicuity of breast tumors in vivo. Under NIR laser irradiation, AgPCPP nanoparticles significantly reduce breast tumor growth, leading to prolonged survival compared to free Ag2S-NP. Over time, AgPCPP retention in tissues gradually decreases, without any signs of acute toxicity, providing strong evidence of their safety and biodegradability. Therefore, AgPCPP may serve as a "one-for-all" theranostic agent that degrades into small components for excretion after fulfilling diagnostic and therapeutic tasks, offering good prospects for clinical translation.

Polyionic vaccine adjuvants: another look at aluminum salts and polyelectrolytes.

Adjuvants improve the adaptive immune response to a vaccine antigen by modulating innate immunity or facilitating transport and presentation. The selection of an appropriate adjuvant has become vital as new vaccines trend toward narrower composition, expanded application, and improved safety. Functionally, adjuvants act directly or indirectly on antigen presenting cells (APCs) including dendritic cells (DCs) and are perceived as having molecular patterns associated either with pathogen invasion or endogenous cell damage (known as pathogen associated molecular patterns [PAMPs] and damage associated molecular patterns [DAMPs]), thereby initiating sensing and response pathways. PAMP-type adjuvants are ligands for toll-like receptors (TLRs) and can directly affect DCs to alter the strength, potency, speed, duration, bias, breadth, and scope of adaptive immunity. DAMP-type adjuvants signal via proinflammatory pathways and promote immune cell infiltration, antigen presentation, and effector cell maturation. This class of adjuvants includes mineral salts, oil emulsions, nanoparticles, and polyelectrolytes and comprises colloids and molecular assemblies exhibiting complex, heterogeneous structures. Today innovation in adjuvant technology is driven by rapidly expanding knowledge in immunology, cross-fertilization from other areas including systems biology and materials sciences, and regulatory requirements for quality, safety, efficacy and understanding as part of the vaccine product. Standardizations will aid efforts to better define and compare the structure, function and safety of adjuvants. This article briefly surveys the genesis of adjuvant technology and then re-examines polyionic macromolecules and polyelectrolyte materials, adjuvants currently not known to employ TLR. Specific updates are provided for aluminum-based formulations and polyelectrolytes as examples of improvements to the oldest and emerging classes of vaccine adjuvants in use.

Effect of environmental factors on hydrolytic degradation of water-soluble polyphosphazene polyelectrolyte in aqueous solutions.

Degradation of a water-soluble polyphosphazene, poly[di(carboxylatophenoxy)phosphazene], disodium salt (PCPP) has been studied in aqueous solutions at elevated temperature. This synthetic polyelectrolyte is of interest as vaccine adjuvant and its degradability constitutes an important component of its safety and formulation stability profiles. The degradation process is manifested by a gradual reduction in the molecular weight of the polymer and cleavage of side groups, which is consistent with previously reported data on hydrolytical breakdown of water-soluble polyphosphazenes. The kinetics of hydrolytical degradation exhibits distinct pH dependence and the process is faster in solutions with lower pH. Remarkably, a number of hydrogen bond forming additives, such as polyethylene glycol and Tween displayed a dramatic accelerating effect on the degradation of PCPP, whereas inorganic salts, such as sodium chloride and potassium chloride, showed a trend for its retardation. The results can be potentially explained on the basis of acid promoted hydrolysis mechanism and macromolecular interactions in the system.