Core­shell type thermo­nanoparticles loaded with temozolomide combined with photothermal therapy in melanoma cells.

A novel core­shell type thermo­nanoparticle (CSTNP) co­loaded with temozolomide (TMZ) and the fluorescein new indocyanine green dye IR820 (termed IT­CSTNPs) was designed and combined with a near­infrared (NIR) laser to realize its photothermal conversion. The IT­CSTNPs were prepared using a two­step synthesis method and comprised a thermosensitive shell and a biodegradable core. IR820 and TMZ were entrapped in the shell and the core, respectively. Dynamic light scattering results demonstrated that the average hydrodynamic size of the IT­CSTNPs was 196.4±3.1 nm with a ζ potential of ­24.9±1.3 mV. The encapsulation efficiencies of TMZ and IR820 were 6.1 and 16.6%, respectively. Temperature increase curves under NIR laser irradiation indicated that the IT­CSTNPs exhibited the desired photothermal conversion efficiency. The in vitro drug release curves revealed a suitable release capability of IT­CSTNP under physiological conditions, whereas NIR laser irradiation accelerated the drug release. Inverted fluorescence microscopy and flow cytometry results revealed that the uptake of IT­CSTNPs by A375 melanoma cells occurred in a concentration­dependent manner. Confocal laser scanning microscopy results indicated that IT­CSTNPs entered tumour cells via endocytosis and were located in intercellular lysosomes. In summary, the present study explored the photothermal conversion capability, cellular uptake, and intracellular localization of IT­CSTNPs.

Nanoparticle-based photothermal and photodynamic immunotherapy for tumor treatment.

Nanoparticle-based phototherapies, such as photothermal therapy (PTT) and photodynamic therapy (PDT), exhibit strong efficacy, minimal invasion and negligible side effects in tumor treatment. These phototherapies have received considerable attention and been extensively studied in recent years. In addition to directly killing tumor cells through heat and reactive oxygen species, PTT and PDT can also induce various antitumor effects. In particular, the resultant massive tumor cell death after PTT and PDT triggers immune responses, including the redistribution and activation of immune effector cells, the expression and secretion of cytokines and the transformation of memory T lymphocytes. The antitumor effects can be enhanced by immune checkpoint blockage therapy. This article reviewed the recent advances of nanoparticle-based PTT and PDT, summarized the studies on nanoparticle-based photothermal and photodynamic immunotherapies in vitro and in vivo, and discussed challenges and future research directions.

Enhanced anti-tumor efficacy of temozolomide-loaded carboxylated poly(amido-amine) combined with photothermal/photodynamic therapy for melanoma treatment.

Chemotherapy is an important treatment for malignant tumors; however, its efficacy and clinical application are limited by its side effects and drug resistance properties. Chemotherapy and phototherapy exhibit synergistic anti-tumor effects. In the present study, a carboxylated poly(amido-amine) (PAMAM) with low cytotoxicity was synthesized as a delivery nanocarrier for loading chemotherapeutic drugs, temozolomide (TMZ), and fluorescent dye indocyanine green (ICG). Hyaluronic acid (HA), which targets the CD44-overexpressing cancer cells, was modified on the nanocarrier surface to enhance the selective killing of melanoma cells. Temperature effect and singlet oxygen production experiments showed that the ICG-loaded nanoparticles exhibited good capability to generate heat and singlet oxygen under near-infrared (NIR) light (808 nm) irradiation. In vivo imaging measurement confirmed that the ICG-encapsulated nanoparticle was delivered successfully and effectively accumulated in the tumor site. In vitro and in vivo experiments revealed that the joint application of TMZ- and ICG-loaded nanoparticle can kill melanoma cells and suppress growth after NIR light irradiation. Thus, HA-modified carboxylated PAMAM loaded with TMZ and ICG serves as a promising nanoplatform for melanoma treatment.

Multifunctional near-infrared dye-magnetic nanoparticles for bioimaging and cancer therapy.

Theranostics based on nanoparticles have developed rapidly in the past decade and have been widely used in the diagnosis and treatment of liver cancer, breast cancer, and other tumors. However, for skin cancers, there are limited studies. In the present study, we successfully synthesized a theranostic nanoparticle by grating IR820 onto the surface of chitosan-coated magnetic iron oxide, IR820-CS-Fe3O4, showing an excellent magnetic resonance imaging (MRI) capability and cytotoxic effects against melanoma under irradiation with a near-infrared (NIR) laser (808 nm) in vitro. Furthermore, good stability for up to 8 days and negligible cytotoxicity were observed. These characteristics are important for biomedical applications of nanoparticles. In conclusion, we provide a novel and potential theranostic platform for melanoma treatment and detection.

Superstable Magnetic Nanoparticles in Conjugation with Near-Infrared Dye as a Multimodal Theranostic Platform.

Near-infrared (NIR) dyes functionalized magnetic nanoparticles (MNPs) have been widely applied in magnetic resonance imaging (MRI), NIR fluorescence imaging, drug delivery, and magnetic hyperthermia. However, the stability of MNPs and NIR dyes in water is a key problem to be solved for long-term application. In this study, a kind of superstable iron oxide nanoparticles was synthesized by a facile way, which can be used as T1 and T2 weighted MRI contrast agent. IR820 was grafted onto the surface of nanoparticles by 6-amino hexanoic acid to form IR820-CSQ-Fe conjugates. Attached IR820 showed increased stability in water at least for three months and an enhanced ability of singlet oxygen production of almost double that of free dyes, which will improve its efficiency for photodynamic therapy. Meanwhile, the multispectral optoacoustic tomography (MSOT) and NIR imaging ability of IR820-CSQ-Fe will greatly increase the accuracy of disease detection. All of these features will broaden the application of this material as a multimodal theranostic platform.