Session Detail

Recent studies have highlighted the combination of immuno-therapy with other conventional treatment modalities, which have the potential to reduce cancer metastasis and improve survival. In this work, a nanoparticle (NP) system that was composed of polyaniline-conjugated glycol chitosan (PANI-GCS) was prepared to encapsulate an insoluble toll-like re-ceptor (TLR) 7/8 ligand for combinational photothermal immunotherapy. The hydrophobic PANI was covalently grafted on the hydrophilic GCS via its highly reactive amine groups to form an amphiphilic polymer (PANI-GCS), which could self-assemble into NPs in an aqueous milieu. The conju-gated PANI can be utilized as nano-localized heat sources, remotely controlled by using near-infrared (NIR) light, for cancer cell ablation, while TLR7/8 ligand was applied to in-duce potent inflammatory cytokine secretion by dendritic cells (DC), which may subsequently enhance the activation of anti-gen-specific T cell responses. Our TEM images reveal that the size of the TLR7/8 ligand-loaded PANI-GCS NPs was approx-imately 170 nm, which could be effectively internalized by bone-marrow derived dendritic cells (BMDC), resulting in the upregulation of cell surface costimulatory molecules (CD80 and CD86). In the animal study, we found that intratumoral injection of the PANI-GCS NPs was able to generate localized heat upon exposure to NIR and partially suppress the growth of CT26 tumor cells in a mouse model. Additionally, the in-jected TLR7/8 ligand-loaded PANI-GCS NPs could success-fully trigger a long-term systemic antitumor immunity and reject the rechallenged CT26 tumors.

 

In vitro data demonstrated enhanced uptake of angiopep-2 decorated hybrid nanoparticles (ANG-IMNPs) by murine astrocytoma cells (ALTS1C1) and pronounced cytotoxicity by combined NIR-triggered photodynamic therapy (PDT) and photothermal therapy (PTT). In consistence with the increased penetration of ANG-IMNPs through endothelial monolayer in vitro, the NPs have also shown significantly enhanced accumulation at brain tumor by IVIS. The IHC　tissue　examination confirmed prominent apoptotic and necrotic effects on tumor cells in mice receiving targeted dual photo-based therapies, which also led to enhanced median survival (24 days) as compared to the NP treatment without angiopep-2 (14 days).

 

Atherosclerosis is a multifactorial inflammatory disease that would progress silently for long period, and it is also widely accepted as the main cause of cardiovascular diseases. To prevent atherosclerotic plaques generating, imaging early molecular markers and quantifying the extent of disease pro-gression are desired. During the inflammation, circulating monocytes leave the bloodstream and migrate into incipient lipid accumulation in the artery wall, following conditioning by local growth factors and proinflammatory cytokines; therefore, monocyte accumulation in the arterial wall can be observed in fatty streaks, rupture-prone plaques, and experi-mental atherosclerosis. In this work, we synthesized mono-cyte-targeting iron oxide magnetic nanoparticles (MNPs), which were incorporated with the peptides derived from the chemokine receptor CCR2-binding motif of monocytes chem-oattractant protein-1 (MCP-1) as diagnostic tools for poten-tial atherosclerosis. MCP-1-motif MNPs had co-localized with monocytes in in vitro fluorescence imaging. In addition, with MNPs injection in ApoE knock-out mice (ApoE KO mice), the well-characterized animal model of atherosclerosis, MNPs were found in specific organs or regions which had monocytes accumulation, especially the aorta of atherosclerosis model mice, through the in vivo imaging system (IVIS) imaging and magnetic resonance imaging (MRI). We also performed the Oil Red O staining and Prussian Blue staining to confirm the colocalization of MCP-1-motif MNPs and atherosclerosis. The results showed the promising potential of MCP-1-motif MNPs as a diagnostic agent of atherosclerosis.

 

With the appearance of vancomycin 3.0, a super-antibiotic which is more potent than its predecessor vancomycin 1.0, it is implicated that the bacteria are continuously transforming to be equipped with higher drug resistance that greatly raises the difficulty of anti-microbiome. To build up an efficacious treatment approach, we developed a type of perfluorocarbon (PFC)–based nano-emulsions that incorporated photosensitizer (Indocyanine green; ICG), antibiotics (Rifampicin; RIF) and capability of inducing probiotic activity (ICG-RIF-loaded PFC nanoemulsions; IRPNEs). The antibacterial capability of the IRPNEs is aimed to carry out through first stage of growth inhibition due to induction of probiotic fermentation, second stage of photodynamic effect functioned by encapsulated ICG, and the last stage of Rifampicin-mediated antibiotic treatment that is so-called photochemobiotic therapy. For the physical characterization, by dynamic light scattering analysis, the size and surface charge of IRPNEs are 240.7 ± 6.73 nm and -20.9 ± 2.40 mV, respectively. The encapsulation efficiencies of ICG and Rifampicin are approximately 95.0% and 54.0%, respectively. In terms of the phototherapeutic efficacy of the agent, under near infrared (NIR) laser exposure (808 nm; 6 W/cm2), IRPNEs enhanced thermal stability, increased production of singlet oxygen and were able to provide appropriate hyperthermia effect comparing to the freely dissolved ICG. P. acnes with 1 × 106 cells/mL can be completely eradicated by S. epidermidis fermentation products followed by treatment of IRPNEs (≥ 20-μM ICG/3.8-μM RIF) with NIR laser exposure for 5 min, whereby the resulted microbial mortality was even higher than that caused by using 16-fold enhanced amount of loaded RIF alone. To summarize, IRPNEs as a nano-carrier enhanced ICG stability, provided carbon sources to probiotics undergo fermentation and improved antimicrobial efficacy compared to same dosage of naked RIF or ICG.