Microenvironment of pancreatic inflammation: calling for nanotechnology for diagnosis and treatment

Abstract

Acute pancreatitis (AP) is a common and life-threatening digestive disorder. However, its diagnosis and treatment are still impeded by our limited understanding of its etiology, pathogenesis, and clinical manifestations, as well as by the available detection methods. Fortunately, the progress of microenvironment-targeted nanoplatforms has shown their remarkable potential to change the status quo. The pancreatic inflammatory microenvironment is typically characterized by low pH, abundant reactive oxygen species (ROS) and enzymes, overproduction of inflammatory cells, and hypoxia, which exacerbate the pathological development of AP but also provide potential targeting sites for nanoagents to achieve early diagnosis and treatment. This review elaborates the various potential targets of the inflammatory microenvironment of AP and summarizes in detail the prospects for the development and application of functional nanomaterials for specific targets. Additionally, it presents the challenges and future trends to develop multifunctional targeted nanomaterials for the early diagnosis and effective treatment of AP, providing a valuable reference for future research.

Keywords: Acute pancreatitis; Diagnosis; Inflammatory microenvironment; Nanotechnology; Targets; Treatment.

Fig. 1

Schematic diagram of microenvironmental targets of pancreatic inflammation. Compared with normal pancreas, AP is characterized by tissue hypoxia and increases in ROS, enzymes, inflammatory cells, H⁺, and microorganisms, creating an inflammatory microenvironment that exacerbates the pancreatic dysfunction. Therefore, the formation of an inflammatory microenvironment in AP is a potential target for imaging and therapy with the application of nanomaterials

Fig. 2

A The preparation procedure of Gd-NL and M-Gd-NL based on lipid film method. Reproduced with permission from reference [48]. Copyright 2017, DOVE Medical Press B Schematic representation of Gd-DTPA-Cy5.5-PsLmAb for NIRF and MR imaging of MAP and SAP. Reproduced with permission from reference [49]. Copyright 2020, American Chemical Society C Schematic illustration of the mechanism of activatable chemiluminescent probes. Reproduced with permission from reference [62]. Copyright 2022, John Wiley and Sons D Fabrication and targeted-therapeutic schematics of ND-MMSNs. Reproduced with permission from reference [63]. Copyright 2018, Springer Nature E Schematic illustration of nanoparticle-encapsulated CQ/TAM combined with MSCs for arresting the increasing severity of AP in mice through iNOS (IDO) signaling. Reproduced with permission from reference [68]. Copyright 2022, Elsevier

Fig. 3

A Schematic illustration of the self-assembly of ROS-responsive nanoparticles for bioimaging and targeted therapy. Reproduced with permission from reference [79]. Copyright 2021, BIOMED CENTRAL B Schematic illustration of the preparation of poly (ethylene glycol)-block-poly (propylene sulfide) (PEPS) and the therapeutic mechanism of action of ROS-sensitive micelles in vivo. Reproduced with permission from reference [81]. Copyright 2022, Elsevier C Schematic illustration of the therapeutic mechanism by which PBzyme prophylactically treats AP by inhibiting activation of the TLR/NF-κB signaling pathway. Reproduced with permission from reference [17]. Copyright 2021, Ivyspring International Publisher D Schematic diagram of the steps of synthesis of MoSe2-PVP NPs and the therapeutic mechanism for alleviating AP by scavenging RONS. Reproduced with permission from reference [89]. Copyright 2022, BIOMED CENTRAL

Fig. 4

A Representative MRI of SD rats before and after the tail vein injection of Gd-DTPA-FA. Reproduced with permission from reference [96]. Copyright 2014, Elsevier B Schematic graph of bilirubin loaded silk fibroin nanoparticles (BRSNPs) for the experimental AP application. Reproduced with permission from reference [97]. Copyright 2020, Elsevier C Schematic representation of MΦ-NP(L&K) designed to inhibit PLA2 during AP progression. Reproduced with permission from reference [99]. Copyright 2021, Springer Nature

Fig. 5

A SPIO@SiO₂@MnO₂ shows weak T₁ and T₂ contrast intensity in normal physiological conditions, as the T₂ signal of SPIO is quenched by the MnO₂ layer. In the acidic environment of a tumor or inflamed tissue, the MnO₂ layer will decompose into magnetically active Mn²⁺ (T1-weighted), and the T₁ and T₂ signals are sequentially recovered. Reproduced with permission from reference [104]. Copyright 2022, Springer Nature B The cumulative release of COSs from COS@SiO₂ at pH 7.4 and pH 8.0. Reproduced with permission from reference [105]. Copyright 2020, Frontiers Media S.A. C Schematic illustration of biodegradation, ROS scavenging effects, and enhanced theranostic functions by Fe/Ce-MSN-PEG NPs. Reproduced with permission from reference [108]. Copyright 2022, Frontiers Media S.A

Fig. 6

Schematic diagram of different modes of interaction between nanoparticles and targets in the inflammatory microenvironment. Nanoparticles are released from blood vessels into the pancreatic inflammatory microenvironment, which not only react with reduced oxygen and excess enzymes, ROS, and H⁺ to release imaging agents and drugs for diagnostic and therapeutic purposes, but also act directly on these targets to reduce ROS and enzymes and increase oxygen. Additionally, inflammatory cells and bacteria can phagocytose nanoparticles for imaging and exert anti-inflammatory and antibacterial effects. Meanwhile, M1 macrophages were shown to be regulated to M2 macrophages by the action of nanoparticles and changes in the microenvironment. The application of nanotechnology can monitor and reduce the severity of acute pancreatitis