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.
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...
Objective Nanotechnology-based photodynamic therapy (PDT) is a relatively new anti-tumor strategy. However, its efficacy is limited by the hypoxic state in the tumor microenvironment. In the present study, a poly(lactic-co-glycolic acid) (PLGA) nanoparticle that encapsulated both IR820 and catalase (CAT) was developed to enhance anti-tumor therapy. Materials and Methods HA-PLGA-CAT-IR820 nanoparticles (HCINPs) were fabricated via a double emulsion solvent evaporation method. Dynamic light scattering (DLS), transmission electron microscopy (TEM), laser scanning confocal microscopy, and an ultraviolet spectrophotometer were used to identify and characterize the nanoparticles. The stability of the nanoparticle was investigated by DLS via monitoring the sizes and polydispersity indexes (PDIs) in water, PBS, DMEM, and DMEM+10%FBS. Oxygen generation measurement was carried out via visualizing the oxygen bubbles with ultrasound imaging system and an optical microscope. Inverted fluorescence microscopy and flow cytometry were used to measure the uptake and targeting effect of the fluorescent-labeled nanoparticles. The live-dead method and tumor-bearing mouse models were applied to study the HCINP-induced enhanced PDT effect. Results The results showed that the HCINPs could selectively target melanoma cells with high expression of CD44, and generated oxygen by catalyzing H 2 O 2 , which increased the amount of singlet oxygen, ultimately inhibiting tumor growth significantly. Conclusion The present study presents a novel nanoplatform for melanoma treatment.
BackgroundTemozolomide (TMZ) is widely used to treat melanoma; however, response rates to TMZ are low because of rapid and frequent resistance. Conditionally, replicative adenoviruses (CRAds) are an effective and promising approach. The receptor for adenovirus is coxsackie‐adenovirus receptor (CAR), which is poorly expressed in most cells. However, CD46, which is the receptor of species B adenoviruses (Ads), is highly expressed in many cells.MethodsWe constructed CRAd F5/35‐ZD55‐IL‐24, which uses the viral receptors CAR and CD46 for entry into cells. We investigated the antitumor effect of F5/35‐ZD55‐IL‐24 in combination with TMZ to treat melanoma in vitro and in vivo.ResultsThe \results indicated that F5/35‐ZD55‐IL‐24 in combination with TMZ produced additive or synergistic antitumor and pro‐apoptotic effects in melanoma cells. The combination of F5/35‐ZD55‐IL‐24 and TMZ significantly inhibited the growth of melanoma in vivo. In addition, the antitumor effect of F5/35‐ZD55‐IL‐24 was superior to that of ZD55‐IL‐24 and ZD55‐IL‐24 combined with TMZ.ConclusionsThe use of F5/35‐ZD55‐IL‐24 in conjunction with TMZ is a promising approach for anti‐melanoma therapy.Our results indicated that F5/35‐ZD55‐IL‐24 in combination with TMZ produced additive or synergistic antitumor effect and pro‐apoptotic effect in melanoma cells highly expressed CD46. The combination of F5/35‐ZD55‐IL‐24 and TMZ significantly inhibited the growth of melanoma in vivo. We also found the antitumor effect of F5/35‐ZD55‐IL‐24 was superior to ZD55‐IL‐24, the combination of F5/35‐ZD55‐IL‐24 and TMZ had a more significant antitumor effect than ZD55‐IL‐24 combining with TMZ.
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