Tumor targeted mesoporous silica-coated gold nanorods facilitate detection of pancreatic tumors using Multispectral optoacoustic tomography

Multispectral optoacoustic tomography （MSOT） is an emerging imaging technology that offers several advantages over traditional modalities, particularly in its ability to resolve optical contrast at depth on the microscopic scale. While potential applications include the early detection of tumors below clinical thresholds set by current technology, the lack of tumor-specific contrast agents limits the use of MSOT imaging. Therefore, we constructed highly stable nano-contrast agents by coating gold nanorods （GNRs） with either polyacrylic acid （PAA） or amine- functionalized mesoporous silica （MS）. Syndecan-1, which has been shown to target insulin-like growth factor 1 receptor （IGF1-R） （upregulated in pancreatic tumors）, was conjugated on the surface of PAA-coated GNRs （PAA-GNRs） or MS-coated GNRs （MS-GNRs） to create tumor-targeted nanoparticles. In vitro, tumor targeting of nanoparticles was assessed with flow cytometry. In S2VP10L cells （positive for IGF1-R）, the syndecan-1 MS-GNRs （Syndecan-MS-GNRs） demonstrated an increase in OA signal, 10x, compared to syndecan-1 PAA- GNRs （Syndecan-PAA-GNRs）. Minimal binding was observed in MiaPaca-2 cells （negative for IGF1-R）. In vivo, tumor specific targeting of Syndecan-MS-GNRs was evaluated using a murine orthotopic pancreatic cancer model. The Syndecan- MS-GNRs demonstrated significantly greater accumulation within pancreatic tumors than in off-target organs such as the liver. Mice implanted with the IGF1-R negative MiaPaca-2 cells did not demonstrate specific tumor targeting. In summary, we report that targeted nano-contrast agents （Syndecan-MS-GNRs） can successfully detect orthotopic pancreatic tumors with minimum off-target binding in vivo using MSOT.

A multifunctional nanoaggregate-based system for detection of rheumatoid arthritis via Optoacoustic/NIR-Ⅱ fluorescent imaging and therapy via inhibiting JAK-STAT/NF-κB/NLRP3 pathways

Rheumatoid arthritis(RA)is a debilitating autoimmune disease that causes chronic pain and serious complications,presenting a significant challenge to treat.Promising approaches for treating RA involve signaling pathways modulation and targeted therapy.To this end,a multifunctional nanosystem,TPC-U@HAT,has been designed for RA therapy,featuring multitargeting,dual-stimuli response,and on-demand drug release capabilities.TPC-U@HAT is composed of a probe/prodrug TPC,a JAK1 kinase inhibitor upadacitinib,and the drug carrier HAT.TPC is composed of an aggregation-induced emission(AIE)-active NIR-II chromophore TPY and an NF-κB/NLRP3 inhibitor caffeic acid phenethyl ester(CAPE),connected via boronic ester bond which serves as the reactive-oxygen-species-responsive linker.The carrier,HAT,is created by grafting bone-targeting alendronate and hydrophobic tocopheryl succinate onto hyaluronic acid chains,which can encapsulate TPC and upadacitinib to form TPC-U@HAT.Upon intravenous injection into mice,TPC-U@HAT accumulates at inflamed lesions of RA through both active and passive targeting,and the overexpressed hyaluronidase and H_(2)O_(2) therein cleave the hyaluronic acid polymer chains and boronate bonds,respectively.This generates an AIE-active chromophore for detection and therapeutic evaluation of RA via both optoacoustic imaging and NIR-II fluorescent imaging and concomitantly releases CAPE and upadacitinib to exert efficacious therapy by inhibiting NF-κB/NLRP3 and JAK-STAT pathways.