Multimodal imaging and photothermal synergistic immunotherapy of retinoblastoma with tuftsin-loaded carbonized MOF nanoparticles

Abstract

Retinoblastoma (Rb) represents 3% of all childhood malignancies and seriously endangers children's lives and quality of life. Early diagnosis and treatment can save children's vision as much as possible. Multifunctional nanoparticles have become a research hotspot in recent years and are expected to realize the integration of early diagnosis and early treatment. Therefore, we report a nanoparticle with dual-mode imaging, photothermal therapy, and immune activation: carbonized MOF nanoparticles (CM NPs) loaded with the immune polypeptide tuftsin (CMT NPs). The dual-mode imaging ability, antitumor effect, and macrophage immunity activation ability of these nanoparticles combined with laser irradiation were studied. The biosafety of CMT NPs was detected. The multifunctional magnetic nanoparticles enhanced photoacoustic (PA) and magnetic resonance (MR) imaging in vivo and in vitro , facilitating diagnosis and efficacy evaluation. The combined effect of CMT NPs and laser irradiation was recorded and verified. Through the accumulation of magnetic field nanoparticles in tumors, the photothermal conversion of nanoparticles under laser irradiation led directly to tumor apoptosis/necrosis, and the release of tuftsin induced macrophage M1-type activation, resulting in antitumor immune effects. Enhanced PA/MR imaging CMT NPs have great potential in dual-mode image-guided laser/immune cotherapy. The nanoparticles have high biosafety and have potential in cancer treatment.

Nanoscale metallic‐organic frameworks as an advanced tool for medical applications: Challenges and recent progress

“…Thus, one of the main challenges is to reduce these side effects through targeted delivery of therapeutic agents to cancer cells via three main approaches: (1) Passive targeting, which mainly relies on the enhanced permeability and retention (EPR) phenomenon, (2) active targeting, which uses antibody‐modified vectors with high affinity toward cancerous cells or magnetic targeting, and (3) triggered release, under certain external stimuli such as heat, light, or ultrasounds. [ 36 ]…”

“…Tumors have a microenvironment that includes transformed cells, blood vessels, fibroblasts, and immune cells. [ 36 ] These complex aggregates produce cytokines, which promote the growth of tumor cells and inhibit the immunogenicity and antitumor activity. Immunotherapy is a type of cancer treatment that activates the immune system to change the tumor microenvironment, thus rapidly killing dividing tumor cells.…”

“…The nanoplatform was designed by encapsulating CuS as a photothermal agent and DOX as a therapeutic drug in ZIF‐8 modified with FA and PEG. Zou et al [ 36 ] designed a carbonized nanoscale MOF (Mil‐100 (Fe)) coated with tuftsin (CMT NPs), which had dual‐mode imaging ability of photoacoustic and MRI as well as enhanced immunotherapy–PTT properties. The presence of the iron ion in the MOF caused magnetism that improved targeted transfer of tuftsin as immune polypeptide and MRI‐related property.…”

“…Thus, one of the main challenges is to reduce these side effects through targeted delivery of therapeutic agents to cancer cells via three main approaches: (1) Passive targeting, which mainly relies on the enhanced permeability and retention (EPR) phenomenon, (2) active targeting, which uses antibodymodified vectors with high affinity toward cancerous cells or magnetic targeting, and (3) triggered release, under certain external stimuli such as heat, light, or ultrasounds. [36] Moradi et al [37] used hyaluronic acid (HA)-modified NH 2 -MIL-101 (Fe) for the targeted delivery of platinum and curcumin (CUR). HA has a high affinity to CD44 receptors; hence, HA-based nanoparticles are a good strategy for anticancer therapeutic agent delivery into CD44-overexpressing tumor cells.…”

“…PTT is another approach for cancer treatment suitable for solid tumors based on killing tumor cells by disruption of their membrane, through destruction of the cytoskeleton and inhibiting DNA replication by straight thermal ablation. [36,113,114] Nanomaterials accumulate in tumors and cause localized heat (i.e., around 42 C) through the conversion of laser energy into heat. This heat causes tumor ablation through the vibrational relaxation of the excited photothermal agents, resulting in apoptosis, necroptosis and necrosis of the tumor tissue.…”