Nanoparticle-based delivery systems for cancer immunotherapies aim to improve the safety and efficacy of these treatments through local delivery to specialized antigen-presenting cells (APCs). Multifunctional mesoporous silica nanoparticles (MSNs), with their large surface areas, their tunable particle and pore sizes, and their spatially controlled functionalization, represent a safe and versatile carrier system. In this study, we demonstrate the potential of MSNs as a pH-responsive drug carrier system for the anticancer immune-stimulant R848 (resiquimod), a synthetic Toll-like receptor 7 and 8 agonist. Equipped with a biotin–avidin cap, the tailor-made nanoparticles showed efficient stimuli-responsive release of their R848 cargo in an environmental pH of 5.5 or below. We showed that the MSNs loaded with R848 were rapidly taken up by APCs into the acidic environment of the lysosome and that they potently activated the immune cells. Upon subcutaneous injection into mice, the particles accumulated in migratory dendritic cells (DCs) in the draining lymph nodes, where they strongly enhanced the activation of the DCs. Furthermore, simultaneous delivery of the model antigen OVA and the adjuvant R848 by MSNs resulted in an augmented antigen-specific T-cell response. The MSNs significantly improved the pharmacokinetic profile of R848 in mice, as the half-life of the drug was increased 6-fold, and at the same time, the systemic exposure was reduced. In summary, we demonstrate that MSNs represent a promising tool for targeted delivery of the immune modulator R848 to APCs and hold considerable potential as a carrier for cancer vaccines.
Polydopamine can form biocompatible particles that convert light into heat. Recently, a protocol has been optimized to synthesize polydopamine/protein hybrid nanoparticles that retain the biological function of proteins, and combine it with the stimuli-induced heat generation of polydopamine. We have utilized this novel system to form polydopamine particles, containing transferrin (PDA/Tf). Mouse melanoma cells, which strongly express the transferrin receptor, were exposed to PDA/Tf nanoparticles (NPs) and, subsequently, were irradiated with a UV laser. The cell death rate was monitored in real-time. When irradiated, the melanoma cells exposed to PDA/Tf NPs underwent apoptosis, faster than the control cells, pointing towards the ability of PDA/Tf to mediate UV-light-induced cell death. The system was also validated in an organotypic, 3D-printed tumor spheroid model, comprising mouse melanoma cells, and the exposure and subsequent irradiation with UV-light, yielded similar results to the 2D cell culture. The process of apoptosis was found to be targeted and mediated by the lysosomal membrane permeabilization. Therefore, the herein presented polydopamine/protein NPs constitute a versatile and stable system for cancer cell-targeting and photothermal apoptosis induction.
Polydopamine can form black nanoparticles and has recently been gaining attention due to its extraordinary heating properties upon excitation with light. Herein, polydopamine hybrid nanoparticles are synthesized in different sizes and subsequently added to a solar fluid to analyze heating ability. The solar fluids with the differently sized hybrid polydopamine particles are compared to a solar fluid containing food coloring (i.e., micrometer‐sized soot particles, similar to India Ink) and silver nanoparticles. The hybrid polydopamine nanoparticles are found to heat more efficiently than silver nanoparticles or food coloring, respectively. In addition, no hybrid polydopamine nanoparticle deposits are found in the direct absorption solar collector in comparison to the solar fluids doped with silver nanoparticles or food coloring. Thus, this work shows that hybrid polydopamine nanoparticles are promising candidates to increase the efficiency of solar fluids.
In article number 1900101, Barbara Rothen‐Rutishauser and co‐workers dope solar fluids used in solar thermal energy with polydopamine/bovine serum albumin nanoparticles. The solar fluids produced are circulated through a 3D printed collector, whereby the addition of these nanoparticles results in an efficiency temperature increase of the solar fluid compared to soot particle and silver nanoparticle doped fluids.