Theranostic micelles based on upconversion nanoparticles for dual-modality imaging and photodynamic therapy in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is frequently metastatic once diagnosed and less likely to respond to curative surgery, emphasizing the need for the development of more sensitive and effective diagnostic and therapeutic strategies. Epithelial cell adhesion molecule (EpCAM) is deemed as the biomarker of cancer stem cells (CSCs), which are mainly responsible for the recurrence, metastasis and prognosis of HCC. In this study, we discuss the use of mitoxantrone (MX), an antitumor drug and a photosensitizer, for designing upconversion nanoparticle-based micelles grafted with the anti-EpCAM antibody, for dual-modality magnetic resonance/upconversion luminescence (MR/UCL)-guided synergetic chemotherapy and photodynamic therapy (PDT). The obtained micelles exhibit good biocompatibility, high specificity to HCC cells and superior fluorescent/magnetic properties in vitro. In vivo results demonstrate that the targeted micelles exhibited much better MR/UCL imaging qualities compared to the nontargeted micelles after the intravenous injection. More importantly, PEGylated UCNP micelles loaded with MX and grafted with anti-EpCAM antibody, denoted as anti-EpCAM-UPGs-MX, showcased the most effective synergetic antitumor efficacy compared with other treatment groups both in vitro and vivo. The remarkable antitumor effect, coupled with superior simultaneous dual-modality MR/UCL imaging as well as good biocompatibility and negligible toxicity, makes the UPG micelles promising for future translational research in HCC diagnosis and therapy.

Lanthanide-Doped Upconversion Nanocarriers for Drug and Gene Delivery

“…Increasing the concentration of nanocarriers induces high toxicity in normal tissues. Thus, to overcome these limitations, further studies on drug/gene delivery systems that combine immunotherapy [ 90 ] or other therapies, such as photodynamic therapy (PDT) [ 91 , 92 ] or photothermal therapy (PTT) [ 93 ], have been reported. Researchers should also investigate and understand the leakage of drugs/genes from the cargo to prevent side effects.…”

<p>Magnetite Nanoparticles and Spheres for Chemo- and Photothermal Therapy of Hepatocellular Carcinoma in vitro</p>

“…Therefore, there are big expectations for nanotechnology, which is supposed to increase the efficiency of existing methods and develop novel alternative modalities, reducing or avoiding unwanted side effects and toxicity to healthy cells. [8][9][10][11] This is mostly realized by tailoring and synthesis of multimodal drug carriers for anticancer therapy based on nanomaterials. Two of the most promising nanomaterials employed in the field of multifunctional nanomaterials for cancer treatment are magnetic nanoparticles (NPs) and spheres (sMAG) of iron oxides.…”

Recent progress in nanotechnology-based novel drug delivery systems in designing of cisplatin for cancer therapy: an overview

“…Nanocarrier-based delivery of several anti-cancer drugs has gained more attention in the past decades because of its selective targeting, improved drug efficacy, lower systemic toxicity, cellular uptake and accumulation inside the tumour, particularly on the improvement of the enhanced permeability and retention (EPR) effect [2]. Meanwhile, nanotechnology is also used for cancer detection, biomedical imaging and disease monitoring [3]. The standardized definition of nanoparticles (NPs) is that it has a spherical shape whose size is considered one, two and three dimensions, having the diameter size of 1-100 nm [4].…”