Application of phototherapeutic-based nanoparticles in colorectal cancer

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death, which accounts for approximately 10% of all new cancer cases worldwide. Surgery is the main method for treatment of early-stage CRC. However, it is not effective for most metastatic tumors, and new treatment and diagnosis strategies need to be developed. Photosensitizers (PSs) play an important role in the treatment of CRC. Phototherapy also has a broad prospect in the treatment of CRC because of its low invasiveness and low toxicity. However, most PSs are associated with limitations including poor solubility, poor selectivity and high toxicity. The application of nanomaterials in PSs has added many advantages, including increased solubility, bioavailability, targeting, stability and low toxicity. In this review, based on phototherapy, we discuss the characteristics and development progress of PSs, the targeting of PSs at organ, cell and molecular levels, and the current methods of optimizing PSs, especially the application of nanoparticles as carriers in CRC. We introduce the photosensitizer (PS) targeting process in photodynamic therapy (PDT), the damage mechanism of PDT, and the application of classic PS in CRC. The action process and damage mechanism of photothermal therapy (PTT) and the types of ablation agents. In addition, we present the imaging examination and the application of PDT / PTT in tumor, including (fluorescence imaging, photoacoustic imaging, nuclear magnetic resonance imaging, nuclear imaging) to provide the basis for the early diagnosis of CRC. Notably, single phototherapy has several limitations in vivo, especially for deep tumors. Here, we discuss the advantages of the combination therapy of PDT and PTT compared with the single therapy. At the same time, this review summarizes the clinical application of PS in CRC. Although a variety of nanomaterials are in the research and development stage, few of them are actually on the market, they will show great advantages in the treatment of CRC in the near future.

Keywords: colorectal cancer; nanoparticle.; photodynamic therapy; photosensitizer; photothermal therapy.

Figure 1

Structure and Function mechanism of nMOF. (A) Schematic showing the RT and RDT process enabled by Hf-DBB-Ru.6 (B) The process of Mitochondria-targeted RT-RDT mediated by Hf-DBB-Ru .

Figure 2

PGE2 regulates tumor microenvironment. PGE2 inhibits the activation of dendritic cells and B cells, and induce the activation or formation of M2 polarized macrophages, myeloid suppressor cells (MDSCs) tumor associated fibroblasts and mast cells .

Figure 3

Signaling pathway of BCL-2. Under the pressure, the expression of BH3 increased, which further blocked the expression of Bcl-2, inactivated Bax/Bak, and resulted in the closure of MOMP and apoptosis

Figure 4

Epidermal growth factor receptor (EGFR) signaling pathway and potential mechanism of resistance to cetuximab and panitumumab .

Figure 5

Mechanism of photodynamic reaction and targets of ROS singlet ground state. The Ps transits from singlet ground state to triplet ground state and produces ROS through type I reaction, and ROS can mediate tumor cell death by acting on various organelles and tumor microvessels.

Figure 6

Schematic of apoptotic and autophagic signaling upon ROS. ROS can activate Apoptosis Signal Regulating Kinase 1 (ASK1) by activating sulfur peroxide protein, ASK1 can regulate protein phosphorylation of JNK, ASK1 can activate Bax and Bak or increase the expression of p53 through Bim and BMF to initiate apoptosis. H₂O₂ activated ATM independently by MRN/ser-1981. Activated ATM induces apoptosis and autophagy through CHK2/p53 and LKB1/AMPK/ TSC2/ mTORC1 pathways respectively .

Figure 7

Molecular structure formula of some PSs.

Figure 8

Schematic diagram of multimodal targeted PTT nanomedicine.