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.
Tumor treatment is still complicated in the field of medicine. Tumor immunotherapy has been the most interesting research field in cancer therapy. Application of chimeric antigen receptor T (CAR-T) cell therapy has recently achieved excellent clinical outcome in patients, especially those with CD19-positive hematologic malignancies. This phenomenon has induced intense interest to develop CAR-T cell therapy for cancer, especially for solid tumors. However, the performance of CAR-T cell treatment in solid tumor is not as satisfactory as that in hematologic disease. Clinical studies on some neoplasms, such as glioblastoma, ovarian cancer, and cholangiocarcinoma, have achieved desirable outcome. This review describes the history and evolution of CAR-T, generalizes the structure and preparation of CAR-T, and summarizes the latest advances on CAR-T cell therapy in different tumor types. The last section presents the current challenges and prospects of CAR-T application to provide guidance for subsequent research.
Ultraviolet (UV) irradiation, particularly ultraviolet A (UVA), stimulates reactive oxygen species (ROS) production in the epidermis and dermis, which plays a major part in the photoageing of human skin. Several studies have demonstrated that cerium oxide nanoparticles (CeO 2 NP) can exhibit an antioxidant effect and free radical scavenging activity. However, the protective role of CeO 2 NP in skin photoageing and the underlying mechanisms are unclear. In this study, we investigated the effects of CeO 2 NP on UVA-irradiated human skin fibroblasts (HSFs) and explored the potential signalling pathway. CeO 2 NP had no apparent cytotoxicity, and could reduce the production of proinflammatory cytokines, intracellular ROS, senescence-associated β-galactosidase activity, and downregulate phosphorylation of c-Jun N-terminal kinases (JNKs) after exposure to UVA radiation. Based on our findings, CeO 2 NPs have great potential against UVA radiation-induced photoageing in HSFs via regulating the JNK signal-transduction pathway to inhibit oxidative stress and DNA damage.
RNA interference (RNAi) and clustered regularly interspersed short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) gene-editing technologies have evolved as powerful tools for the regulation of gene expression. The delivery of RNAi molecules into cells via viral or nonviral vectors can induce mRNA molecules to bind to RNAi molecules, decreasing the expression of proteins encoded by the mRNAs, resulting in reduced gene expression [1]. RNAi molecules include small interference RNA (siRNA), microRNA, and short hairpin RNA (shRNA). Of these, siRNA are the most widely used type of RNAi molecules in targeted therapy owing to their potent and specific RNAi-triggering activities [2]. CRISPR/Cas9 gene editing technology is a versatile tool for genomic editing [3] and genomic loci imaging [4]. With the guidance of single guide RNA (sgRNA), which comprise artificially synthesized CRISPR-derived RNA and tracrRNA/crRNA complexes, Cas9 proteins can accurately knock-out/-in, interfere with, activate [5] and mark target genes. When two or more sgRNAs co-express with a single Cas9 protein, the CRISPR/Cas9 system is able to target different genomic loci simultaneously, greatly improving the efficiency of gene editing [6]. sgRNA has a straightforward construction and is easily designed. Based on these excellent qualities, CRISPR/Cas9 systems have been rapidly and extensively applied in the field of genome editing since their inception, providing a novel and efficient tool for gene-targeted therapy [7].However, siRNAs or CRISPR-Cas9 systems may incorrectly bind to untargeted genes and generate unpredictable mutations, mismatches or deletions that are outside the targeted site, leading to cancer and/or other genetic conditions [8]. In addition, most studies based on siRNAs or CRISPR-Cas9 systems rely on viral vectors for plasmid transfection [9]. Regrettably, the use of viral vectors presents certain disadvantages. For instance, viruses are immunogenic and, when expressed in the host, may induce an immune response, thus limiting the practical application of gene perturbation in gene therapy [1]. Thus, the identification of novel vectors with higher safety and improved targeting is desirable for the future development of gene-targeted therapy.Owing to the unique qualities of nanoparticles, such as their nanoscale sizes (10-1000 nm) [10], low toxicity, long cycle time [11] and excellent plasticity, they have been widely researched and applied as drug carriers to treat diseases. Furthermore, nanoparticles show great potential for the delivery of novel gene therapeutic agents including antisense oligonucleotides [12], molecularly targeted agents [13], siRNA [14] and mRNA [15]. Accordingly, increasing numbers of researchers are turning their attention to the application of nanoparticles as vectors for the delivery of siRNA or CRISPR/Cas9 systems for the treatment of cancer and other diseases.Herein, we present a review of the recent advances in nanoparticle-based siRNA and CRISPR/Cas9 delivery systems, both in vitro and in v...
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