Engineered macrophages as near-infrared light activated drug vectors for chemo-photodynamic therapy of primary and bone metastatic breast cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Huang Y
PROVIDER: S-EPMC8280231 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Many drug controlled release methods have been integrated in multifunctional nanoparticles, such as pH-, redox-, temperature-, enzyme-, and light-responsive release. However, few report is associated with the ROS responsive drug controlled release. Herein, a thioketal linker-based ROS responsive drug (camptothecin conjugated with thioketal linker, abbreviated as TL-CPT) was prepared and the thioketal linker could be cleaved by ROS(reactive oxygen species). To achieve cancer simultaneous optical imaging, photodynamic therapy and chemotherapy, the photosensitizer Chlorin e6(Ce6), TL-CPT and carboxyl-mPEG were loaded on the upconversion nanoparticles (UCNPs), which were named as Ce6-CPT-UCNPs. Under 980 nm laser irradiation, Ce6-CPT-UCNPs emitted a narrow emission band at 645-675 nm which was overlapped with Ce6 absorption peak. Ce6 absorbed the light to produce ROS, which was used for photodynamic therapy and to cleave the thioketal linker in Ce6-CPT-UCNPs to release camptothecin for chemotherapy. Meanwhile, Ce6 absorbed the light, was used for near-infrared fluorescence imaging. The in vivo biodistribution studies showed that the prepared nanoparticles had high orthotopic lung cancer targeting efficiency. The in vivo therapeutic results demonstrated that NCI-H460 lung cancers could be completely eliminated by combining chemo- and photodynamic therapy under 980 nm laser irradiation. The prepared multifunctional Ce6-CPT-UCNPs have great potential in applications such as cancer targeted fluorescent imaging, simultaneous ROS activated chemo- and photodynamic therapy in near future.
| S-EPMC4775857 | biostudies-other
Project description:Despite burgeoning development of nanoplatform made in the past few years, it remains a challenge to produce drug nanocarrier that enables requested on/off drug release. Thus, this study aimed to develop an ideal near-infrared light-triggered smart nanocarrier for targeted imaging-guided treatment of cancer that tactfully integrated photothermal therapy with chemotherapy to accurately control drug release time and dosage. Methods: This delivery system was composed of Ag2S QD coating with dendritic mesoporous silica (DMSN), which acted as nanocarrier of doxorubicin localized inside pores. To provide the nanocarrier with controlled release capability, a polypeptide-engineered that structure was reversible to photothermal effect of Ag2S QD, was covalently grafted to the external surface of drug-loaded DMSN. Results: This nanocarrier with the size of 40~60 nm had satisfactory biocompatibility and photothermal conversion efficiency up to 28.35%. Due to acidity-triggered charge reversal of polypeptide, which significantly extended circulation time and improved targeting ability, fluorescence and photoacoustic signals were still obvious at tumor site post-24 h by tail vein injection and chemo-photothermal synergistic therapy obviously enhanced antitumor efficacy. Mild PTT with multiple short-term exposures not only reduced the side effect of overdose drug but also avoided skin damage caused by long-term irradiation. Conclusion: By adjusting irradiation time and on/off cycle, multiple small amount local drug release reduced the side effect of overdose drug and skin damage. This novel approach provided an ideal near-infrared light-triggered nanocarrier with accurate control of area, time, and especially dosage.
| S-EPMC6831479 | biostudies-literature
Project description:Indocyanine green (ICG) has been reported as a potential near-infrared (NIR) photosensitizer for photodynamic therapy (PDT) of cancer. However the application of ICG-mediated PDT is both intrinsically and physiologically limited. Here we report a combination of ICG-PDT with a chemotherapy drug etoposide (VP-16), aiming to enhance the anticancer efficacy, to circumvent limitations of PDT using ICG, and to reduce side effects of VP-16. We found in controlled in vitro cell-based assays that this combination is effective in killing non-small-cell lung cancer cells (NSCLC, A549 cell line). We also found that the combination of ICG-PDT and VP-16 exhibits strong synergy in killing non-small-cell lung cancer cells partially through inducing more DNA double-strand breaks (DSBs), while it has a much weaker synergy in killing human normal cells (GM05757). Furthermore, by studying the treatment sequence dependence and the cytotoxicity of laser-irradiated mixtures of ICG and VP-16, we found that the observed synergy involves direct/indirect reactions between ICG and VP-16. We further propose that there exists an electron transfer reaction between ICG and VP-16 under irradiation. This study therefore shows the anticancer efficacy of ICG-PDT combined with VP-16. These findings suggest that ICG-mediated PDT may be applied in combination with the chemotherapy drug VP-16 to treat some cancers, especially the non-small-cell lung cancer.
| S-EPMC5483882 | biostudies-literature
Project description:A combination of chemo- and photo-thermal therapy (PTT) has provided a promising efficient approach for cancer therapy. To achieve the superior synergistic chemotherapeutic effect with PTT, the development of a simple theranostic nanoplatform that can provide both cancer imaging and a spatial-temporal synchronism of both therapeutic approaches are highly desired. Our previous study has demonstrated that near-infrared (NIR) light-triggered biodegradable chitosan-based amphiphilic block copolymer micelles (SNSC) containing light-sensitive 2-nitrobenzyl alcohol and NIR dye cypate on the hydrophobic block could be used for fast light-triggered drug release. In this study, we conjugated the SNSC micelles with tumor targeting ligand c(RGDyK) and also encapsulated antitumor drug Paclitaxel (PTX). The results show that c(RGDyK)-modified micelles could enhance the targeting and residence time in tumor site, as well as be capable performing high temperature response for PTT on cancer cells and two-photon photolysis for fast release of anticancer drugs under NIR irradiation. In vitro release profiles show a significant controlled release effort that the release concentration of PTX from micelles was significantly increased with the exposure of NIR light. In vitro and in vivo antitumor studies demonstrate that, compared with chemo or PTT treatment alone, the combined treatment with the local exposure of NIR light exhibited significantly enhanced anti-tumor efficiency. These findings indicate that this system exhibited great potential in tumor-targeting imaging and synchronous chemo- and photo-thermal therapy.
| S-EPMC5347683 | biostudies-literature
Project description:Photodynamic therapy (PDT) is a treatment in which photoactive compounds delivered to cancerous tissues are excited with light and then transfer the absorbed energy to adjacent tissue oxygen molecules to generate toxic singlet oxygen (1O2). As 1O2 is produced only where light and photosensitizers (PSs) are combined, PDT holds promise as a minimally invasive, highly selective treatment for certain cancers. The practical application of PDT requires easily synthesized, water-soluble PSs that have low dark toxicities, high 1O2 quantum yields, and efficient absorption of 650-850 nm near-infrared (NIR) light, which deeply penetrates tissue. We recently developed a linear tetrapyrrole metal complex, Pd[DMBil1]-PEG750, that meets most of these criteria. This complex is remarkably effective as a PS for PDT against triple-negative breast cancer (TNBC) cells but, critically, it does not absorb NIR light, which is necessary to treat deeper tumors. To enable NIR activation, we synthesized a new derivative, Pd[DMBil1]-PEG5000-SH, which bears a thiol functionality that facilitates conjugation to NIR-absorbing gold nanoshells (NSs). Upon excitation with pulsed 800 nm light, NSs emit two-photon-induced photoluminescence spanning 500-700 nm, which can sensitize the attached PSs to initiate PDT. Additionally, NSs produce heat upon 800 nm irradiation, endowing the NS-PS conjugates with an auxiliary photothermal therapeutic (PTT) capability. Here, we demonstrate that NS-PS conjugates are potent mediators of NIR-activated tandem PDT/PTT against TNBC cells in vitro. We show that Pd[DMBil1]-PEG5000-SH retains the photophysical properties of the parent Pd[DMBil1] complex, and that NS-PS generate 1O2 under pulsed 800 nm irradiation, confirming activation of the PSs by photoluminescence emitted from NSs. TNBC cells readily internalize NS PS conjugates, which generate reactive oxygen species in the cells upon pulsed NIR irradiation to damage DNA and induce apoptosis. Together, these findings demonstrate that exploiting photoluminescent NSs as carriers of efficient Pd[DMBil1] PSs is an effective strategy to enable NIR light-activated tandem PDT/PTT.
| S-EPMC6964518 | biostudies-literature
Project description:The spatiotemporal stimulation of liposome-liposome or liposome-membrane fusion processes attracts growing interest as a means to mimic cell-cell interactions in nature and for using these processes for biomedical applications. We report the use of o-nitrobenzyl phosphate functionalized-cholesterol tethered nucleic acid-modified liposomes as functional photoresponsive units for inducing, by NIR-irradiation, spatiotemporal liposome-liposome or liposome-membrane fusion processes. The liposomes are loaded with upconversion nanoparticles (UCNPs) and their NIR irradiation (? = 980 nm) yields luminescence at ? = 365 nm, providing a localized light-source to deprotect the o-nitrobenzyl phosphate groups and resulting in the fragmentation of the nucleic acid structures. In one system, the NIR-triggered fusion of two liposomes, L1 and L2, is exemplified. Liposome L1 is loaded with UCNPs and Tb3+ ions, and the liposome boundary is functionalized with a cholesterol-tethered, o-nitrobenzyl phosphate caged hairpin nucleic acid structure. Liposome L2 is loaded with 2,6-pyridinedicarboxylic acid, DPA, and its boundary is modified with a cholesterol-tethered nucleic acid, complementary to a part of the caged hairpin, associated with L1. NIR-irradiation of the L1/L2 mixture resulted in the photocleavage of the hairpin structure, associated with L1, and the resulting fragmented nucleic acid associated with L1 hybridized with the nucleic acid linked to L2, leading to the fusion of the two liposomes. The fusion process was followed by dynamic light scattering, and by monitoring the fluorescence of the Tb3+-DPA complex generated upon the fusion of the liposomes and their exchange of contents (fusion efficiency 30%). In a second system, the fusion of the liposomes L1, loaded with UCNPs and doxorubicin (DOX), with HeLa cancer cells functionalized with nucleic acid tethers, complementary to the hairpin units associated with the boundary of L1, and linked to the MUC-1 receptor sites associated with the HeLa cells, through a MUC-1 aptamer unit is exemplified. The effect of DOX-loaded L1/HeLa cell fusion on the cytotoxicity towards HeLa cells is addressed. The NIR UCNP-stimulated cleavage of the o-nitrobenzyl phosphate caged hairpin units associated with L1 leads to the fragmentation of the hairpin units and the resulting nucleic acid tethers hybridize with the nucleic acid-modified HeLa cells, resulting in the liposome-HeLa cell fusion and the release of DOX into the HeLa cells. Selective spatiotemporal cytotoxicity towards HeLa cells is demonstrated (ca. 40% cell killing within two days). The study presents a comprehensive stepwise set of experiments directed towards the development of NIR-driven liposome-liposome or liposome-membrane fusion processes.
| S-EPMC7441577 | biostudies-literature
Project description:Elucidation of upconversion nanoparticles (UCNPs) that can be excited by near-infrared (NIR) light is an interesting topic in the field of photodynamic therapy (PDT). However, the PDT efficiency of conventional UCNPs is limited due to the low quantum yield and overheating effect of the 980 nm light source. In this study, a light source with a wavelength of 808 nm was used as an excitation source for Nd-doped UCNPs to solve the overheating effect. UCNPs with a core@shell structure (NaYF4:Yb,Er,Nd@NaYF4:Yb,Nd) were synthesized to increase the upconversion emission efficiency. Dual-color emitting Er-doped UCNPs and dual photosensitizers (Chlorin e6 and Rose Bengal) were used for enhanced PDT. Each photosensitizer could absorb red and green emissions of the UCNPs to generate reactive oxygen species (ROS), respectively. The ROS generation in a dual photosensitizer system is significantly higher than that in a single photosensitizer system. Additionally, PDT induces immunogenic apoptosis. In this study, by utilizing a highly efficient PDT agent, PDT-induced apoptosis was studied by biomarker analysis.
| S-EPMC7179334 | biostudies-literature
Project description:The ability to modulate the fluorescence of optical probes can be used to enhance signal-to-noise ratios for imaging within highly autofluorescent environments, such as intact tissues and living organisms. Here, we report two bacteriophytochrome-based photoactivatable near-infrared fluorescent proteins, named PAiRFP1 and PAiRFP2. PAiRFPs utilize haem-derived biliverdin, ubiquitous in mammalian tissues, as the chromophore. Initially weakly fluorescent PAiRFPs undergo photoconversion into a highly fluorescent state with excitation/emission at 690/717 nm following a brief irradiation with far-red light. After photoactivation, PAiRFPs slowly revert back to initial state, enabling multiple photoactivation-relaxation cycles. Low-temperature optical spectroscopy reveals several intermediates involved in PAiRFP photocycles, which all differ from that of the bacteriophytochrome precursor. PAiRFPs can be photoactivated in a spatially selective manner in mouse tissues, and optical modulation of their fluorescence allows for substantial contrast enhancement, making PAiRFPs advantageous over permanently fluorescent probes for in vivo imaging conditions of high autofluorescence and low signal levels.
| S-EPMC3749836 | biostudies-literature
Project description:Carbon monoxide (CO) is an endogenous signaling molecule that controls a number of physiological processes. To circumvent the inherent toxicity of CO, light-activated CO-releasing molecules (photoCORMs) have emerged as an alternative for its administration. However, their wider application requires photoactivation using biologically benign visible and near-infrared (NIR) light. In this work, a strategy to access such photoCORMs by fusing two CO-releasing flavonol moieties with a NIR-absorbing cyanine dye is presented. These hybrids liberate two molecules of CO in high chemical yields upon activation with NIR light up to 820 nm and exhibit excellent uncaging cross-sections, which surpass the state-of-the-art by two orders of magnitude. Furthermore, the biocompatibility and applicability of the system in vitro and in vivo are demonstrated, and a mechanism of CO release is proposed. It is hoped that this strategy will stimulate the discovery of new classes of photoCORMs and accelerate the translation of CO-based phototherapy into practice.
| S-EPMC7693251 | biostudies-literature
Project description:Photodynamic therapy (PDT) is a promising and effective method for tumor therapy that relies on the reactive oxygen species (ROS) produced by photosensitizers at specific wavelengths to inhibit tumor cells. Inorganic semiconductive materials are potential photosensitizers that can excellently absorb ultraviolet light to produce ROS to kill cancer cells. However, this strategy is still limited in terms of practical applications due to the weak penetration of ultraviolet light through biological tissue, as well as the hypoxic tumor microenvironment, largely decreasing ROS generation. In this research, novel PDT agents made with mesoporous lanthanide-semiconductor composites are developed to obtain a remarkable amount of generated ROS under near-infrared (NIR) laser irradiation. Due to the larger size (about 120 nm) of the up-conversion material (UCM) used as the substrate, coated with different amounts of semiconductors with mesoporous morphologies, this platform could emit higher blue emission under a 980 nm laser. Meanwhile, both of the semiconductors (SnO2 and TiO2) used have wide absorbance bands in the ultraviolet region, and the ultraviolet fluorescence emitted from the UCM core under NIR laser excitation can be used as the energy donor. Electron transfer processes in SnO2 and TiO2 are generated via the above platforms and produce ROS through photochemical action. Furthermore, the coated semiconductors are mesoporous with larger surface areas (about 302 m2 g-1) and various channels; this is beneficial to obtain enough oxygen to generate more ROS under a hypoxic environment. The PDT efficiency of a typical NaYF4@SnO2 sample is studied using a DPBF detector, in vitro MTT assays, and in vivo tumor inhibition experiments, revealing that this lanthanide-semiconductor platform could be potentially used as a PDT agent under NIR excitation.
| S-EPMC9064574 | biostudies-literature