Embedded Upconversion Nanoparticles in Magnetic Molecularly Imprinted Polymers for Photodynamic Therapy of Hepatocellular Carcinoma

Abstract

Programmed death-ligand 1 protein (PD-L1) is often expressed in various malignant tumors; thus, it is an appropriate marker for targeted cancer therapies. Photodynamic therapy (PDT) uses light and photosensitizers to create singlet oxygen to kill cells. An important approach to PDT is the use of upconversion nanoparticles (UCNPs) to convert near-infrared (NIR) light, which penetrates tissues well, into visible light, allowing PDT to be effective at greater tissue depths. In this work, high-temperature pyrolysis was used to prepare both the core and shell of lanthanide-doped UCNPs with lithium yttrium tetrafluoride (LiYF4) to enhance the green luminescence. The photosensitizer Merocyanine 540 (MC540) was grafted onto the magnetic nanoparticles, and then one peptide sequence from PD-L1 was used as the template and imprinted onto poly(ethylene-co-vinyl alcohol) particles formed by precipitation in a non-solvent. UCNPs in the non-solvent bath were thus entrapped in the imprinted particles to generate composite nanoparticles for the targeting and photodynamic therapy of PD-L1 in tumor cells. Finally, the in vitro cytotoxicity of the nanoparticles in HepG2 human liver cancer cells was evaluated with the continuous administration of MC540/MNPs@MIPs/UCNPs under irradiation by an NIR laser. To understand the delivery of the UCNP-embedded molecularly imprinted polymers, the intrinsic and extrinsic pathways were also investigated.

Molecularly imprinted polymers (MIPs): emerging biomaterials for cancer theragnostic applications

“…Thus, this process achieves efficient PDT without affecting healthy tissue. Lin et al incorporated merocyanine 540 (MC540)-grafted magnetic NPs into MIPs, where the imprinting layer was formed by poly(ethylene-co-vinyl alcohol) (EVAL) via a precipitation method, and entrapped UCNPs in the imprinted particles for exciting the MC540, resulting in catalyzing the generation of ROS [ 163 ]. The PD-L1 peptide sequence (EDLKVQHSSYRQRA) was used as a template to enhance the targeting ability of MIPs against HepG2 human liver cancer cells.…”

“…2 ). A , B , C Reproduced with permission from [ 163 ], published by MDPI 2021. D , E , F , G , H Reproduced with permission from [ 162 ], published by American Chemical Society 2020.…”

Molecularly Imprinted Carriers for Diagnostics and Therapy—A Critical Appraisal

“…Exploiting the magnetic properties of the composite could be another step in the research, possibly allowing for imaging of the synthesized material in an animal model. In a study conducted by the same scientific group [ 76 ], an imprinted magnetic platform of structure and application similar to that previously described was prepared, with additional embedded upconversion nanoparticles that permit using near-infrared light in order to activate the photosensitizer included in the composite ( Figure 6 ). A disadvantage of the composite was the demonstrated elevated cytotoxicity in human hepatoblastoma cells (HepG2) in the absence of a near-infrared light source; although, as was pointed out, this effect could be reduced by modifying the nanoparticles’ surface—a relatively easy method in the design of MIP-based materials.…”

Progress of Nanomaterials in Photodynamic Therapy Against Tumor

“…In addition to the introduction of folate groups, bio-orthogonal labels such as copper-catalyzed azide-alkyne cycloaddition (CuAAC) are also effective methods to improve tumor cell recognition ( Kappenberg et al, 2022 ). Lin et al prepared the first bio-orthogonal two-photon PSs based on Ru (II) complexes by bio-orthogonally labeling Ru-alkynyl-2 Lin C.-C. et al (2021) . In addition to generating ROS to exert cytotoxic effects, it could also exert anti-tumor effects by specifically binding to cancer cell membranes and inducing membrane damage.…”

“…In immunotherapy, ligands that block PD-L1 can also directly prevent PD-1/PD-L1 immune blockade ( Lee et al, 2021 ). Liu and his team modified UCNPs with MIPs formed by Pd-L1 peptide phase transfer imprinting, and prepared MC540/MNPs@MIPs/UCNP composite imprinted particles Lin M. et al (2021) . MC540/MNPs@MIPs/UCNP utilized MIPs to target tumor cells, which improved the binding rate to tumor cells and achieved targeted PDT.…”