ABSTRACT
Photoimmunotherapy (PIT) is an emerging tumor-targeted phototherapy that combines the tumor specificity of monoclonal antibodies with the phototoxicity of light absorbers to rapidly and selectively induce the immunogenic death of target tumor cells. PIT has minimal side effects due to its high specificity. The immunogenic cell death induced by PIT results in rapid maturation of immature dendritic cells proximal to dying tumor cells. Subsequently, the mature dendritic cells present the tumor antigens to CD8+ T cells and induce their activation and proliferation, thus enhancing the antitumor immune response of the host. PIT can also improve the anticancer efficacy by enhancing the penetration of nanomedicines into tumor tissues. In view of the excellent application prospects of PIT, this review summarizes the advances in the immune activation mechanism of PIT, the superenhanced permeability and retention effect, and the new strategies for combinatory therapy, providing references for future research and clinical translation.
Subject(s)
Humans , Antibodies, Monoclonal/therapeutic use , Immunotherapy , Neoplasms/therapy , Photosensitizing Agents , PhototherapyABSTRACT
@#Near infrared photoimmunotherapy (NIR-PIT) is a highly selective molecularly targeted phototherapy for cancer which is based on injecting a conjugate of IRDye700DX,a water-soluble near-infrared silicon-phthalocyanine dye,and a monoclonal antibody that targets an antigen on the cancer cell surface. Subsequent local irradiation of NIR light causes the rapid and specific tumor cell death. Due to the good clinical translation prospects of NIR-PIT,this paper summarizes the influencing factors,antitumor mechanism,main challenges and recent strategies,which may benefit for its research and clinical application.
ABSTRACT
@#The aim of this study was to prepare the nanoconjugates for targeted photodynamic therapy of brain cancer by using eight-arm polyethylene glycol(8PEG)as the carrier and cRGD as the targeting ligand, and to investigate the antitumor effect and its mechanism. UV-Vis spectra and confocal microscopy were used for characterization and cellular uptake behavior of nanoconjugates respectively. Alamar Blue assay and Calcein AM/PI staining were applied to investigate the cytotoxocity of nanoconjugates against tumor cells, and tumor spheroid growth curve was used to assess the tumor growth suppression effect. In addition, the generation of reactive oxygen species(ROS), apoptosis and spheroid permeability test was used to reveal the antitumor mechanism of nanoconjugates. The results showed that cRGD-8PEG-IR700 was taken up efficiently by integrin overexpressed U87MG cells, while almost no uptake was found in integrin free NIH/3T3 cells. Remarkable photokilling effect against U87MG cells was only shown in cRGD-8PEG-IR700 group due to the light-induced ROS generation and apoptosis, whereas growth suppression effect was also observed in U87MG spheroids treated with cRGD-8PEG-IR700 plus light owing to the superior penetration ability of targeted nanoconjugates. Hence, tumor-targeted PEG nanoconjugates may provide a promising drug delivery system for photodynamic therapy of cancers.
ABSTRACT
@#The aim of this study was to prepare albumin nanoparticles by thermal driven self-assembly, and to investigate the formation mechanism, cellular uptake, the kinetics of cellular uptake and intracellular degradation, etc. By measuring the concentrations of thiol, amino and carboxyl groups, the formation mechanism of albumin nanoparticles was revealed. CCK-8 assay was performed to detect the cytotoxicity; inverted fluorescence microscope was used to observe the cellular uptake of the nanoparticles; while the fluorescence resonance energy transfer(FRET)method was applied to investigate the cellular uptake and intracellular degradation kinetics. The drug-loading capacity was investigated using paclitaxel(PTX)as the model drug. The results showed that the albumin nanoparticles produced by thermal driven self-assembly were safe, nontoxic, biodegradable and stabilized by intermolecular disulfide and amide bonds. The drug-loading study indicates that PTX can be highly encapsulated in the nanoparticles. Hence, thermal driven self-assembly method is green and easy to operate, and the albumin nanoparticles can be applied as a new delivery platform for anticancer drugs.