Search

Nowadays various inorganic nanoparticles that generate highly reactive hydroxyl radical (·OH) on the basis of Fenton‐like catalytic activity of metal ions have been designed for chemodynamic therapy. However, the high level of adaptive antioxidants [glutathione (GSH)] in cancer cells could effectively consume ·OH to compromise the treatment efficiency and biosafety of these inorganic nanoparticles, and this is a general concern in chemodynamic therapy. Herein, a new biodegradable nanoscale coordination polymer (NCP) is developed by integration of cisplatin prodrug (DSCP) and iron (III) ions through a reverse microemulsion method. The DSCP in the NCPs could react with GSH to release free cisplatin, while the iron (III) ions could be reduced by GSH into iron (II) to enable Fenton reaction, subsequently leading to amplified intracellular oxidative stress. After surface modification of polyethylene glycol (PEG) and cyclo[Arg‐Gly‐Asp‐D‐Phe‐Lys(mpa)] peptide (cRGD), Fe‐DSCP‐PEG‐cRGD shows an excellent targeting effect against αvβ3‐integrin overexpressed tumor cells. Furthermore, Fe‐DSCP‐PEG‐cRGD enables significant chemo and chemodynamic therapy with dramatically enhanced therapeutic efficiency in comparison to relative monotherapies. Importantly, Fe‐DSCP‐PEG‐cRGD could be efficiently cleared out from mice through feces and urine postinjection 7 days. The NCP presented in this work is simple and economical, which shows great biodegradability and biosafety for potential clinical translation. [ABSTRACT FROM AUTHOR]

Multifunctional biodegradable inorganic theranostic nano-agents are of great interest to the field of nanomedicine. Upon lipid modification, VS2 nanosheets could be converted into ultra-small VS2 nanodots encapsulated inside polyethylene glycol (PEG) modified lipid micelles. Owing to paramagnetism, high near-infrared (NIR) absorbance, and chelator-free 99mTc4+ labeling of VS2, such VS2@lipid-PEG nanoparticles could be used for T1-weighted magnetic resonance (MR), photoacoustic (PA),and single photon emission computed tomography (SPECT) tri-modal imaging guided photothermal ablation of tumors. Importantly, along with the gradual degradation of VS2, our VS2@lipid-PEG nanoparticles exhibit effective body excretion without appreciable toxicity. The unique advantages of VS2 nanostructures with highly integrated functionalities and biodegradable behaviors mean they are promising for applications in cancer theranostics. [ABSTRACT FROM AUTHOR]

Multifunctional biodegradable inorganic theranostic nano-agents are of great interest to the field of nanomedicine. Upon lipid modification, VS2 nanosheets could be converted into ultra-small VS2 nanodots encapsulated inside polyethylene glycol (PEG) modified lipid micelles. Owing to paramagnetism, high near-infrared (NIR) absorbance, and chelator-free 99mTc4+ labeling of VS2, such VS2@lipid-PEG nanoparticles could be used for T1-weighted magnetic resonance (MR), photoacoustic (PA),and single photon emission computed tomography (SPECT) tri-modal imaging guided photothermal ablation of tumors. Importantly, along with the gradual degradation of VS2, our VS2@lipid-PEG nanoparticles exhibit effective body excretion without appreciable toxicity. The unique advantages of VS2 nanostructures with highly integrated functionalities and biodegradable behaviors mean they are promising for applications in cancer theranostics. [ABSTRACT FROM AUTHOR]

Facile preparation of multifunctional theranostic nanoplatforms with well-controlled morphology and sizes remains an attractive in the area of nanomedicine. Here, a new kind of 2D transition metal dichalcogenide, rhenium disulfide (ReS2) nanosheets, with uniform sizes, strong near-infrared (NIR) light, and strong X-ray attenuation, is successfully synthesized. After surface modification with poly(ethylene glycol) (PEG), the synthesized ReS2-PEG nanosheets are stable in various physiological solutions. In addition to their contrasts in photoacoustic imaging and X-ray computed tomography imaging because of their strong NIR light and X-ray absorptions, respectively, such ReS2-PEG nanosheets can also be tracked under nuclear imaging after chelator-free labeling with radioisotope ions, 99mTc4+. Efficient tumor accumulation of ReS2-PEG nanosheets is then observed after intravenous injection into tumor-bearing mice under triple-modal imaging. The combined in vivo photothermal radiotherapy is further conducted, achieving a remarkable synergistic tumor destruction effect. Finally, no obvious toxicity of ReS2-PEG nanosheets is observed from the treated mice within 30 d. This work suggests that such ultrathin ReS2 nanosheets with well-controlled morphology and uniform sizes may be a promising type of multifunctional theranostic agent for remotely triggered cancer combination therapy. [ABSTRACT FROM AUTHOR]

Despite extensive use of radiotherapy in cancer treatment, there has been huge demand to improve its efficacy and accuracy in tumor destruction. To this end, nanoparticle-based radiosensitizers, particularly those with high-Z elements, have been explored to enhance radiotherapy. Meanwhile, imaging is an essential tool prior to the individual planning of precise radiotherapy. Here, hollow tantalum oxide (H-TaOx) nanoshells are prepared using a one-pot template-free method and then modified with polyethylene glycol (PEG), yielding H-TaOx-PEG nanoshells for imaging-guided synergistically enhanced radiotherapy. H-TaOx-PEG nanoshells show strong intrinsic binding with metal ions such as Fe3+ and 99mTc4+ upon simple mixing, enabling magnetic resonance imaging and single photon emission computed tomography imaging, respectively, which are able to track in vivo distribution of those nanoshells and locate the tumor. With mesoporous shells and large cavities, those H-TaOx-PEG nanoshells show efficient loading of 7-ethyl-10-hydroxycamptothecin (SN-38), a hydrophobic chemotherapeutic drug. By means of the radiosensitization effect of Ta to deposit X-ray energy inside tumors, as well as SN-38-induced cell cycle arrest into radiation-sensitive phases, H-TaOx-PEG@SN-38 can offer remarkable synergistic therapeutic outcome in the combined chemoradiotherapy. Without appreciable systemic toxicity, such hollow-TaOx nanostructure may therefore find promising applications in multimodal imaging and enhanced cancer radiotherapy. [ABSTRACT FROM AUTHOR]

Molybdenum oxide (MoOx) nanosheets with high near-infrared (NIR) absorbance and pH-dependent oxidative degradation properties were synthesized, functionalized with polyethylene glycol (PEG), and then used as a degradable photothermal agent and drug carrier. The nanosheets, which are relatively stable under acidic pH, could be degraded at physiological pH. Therefore, MoOx-PEG distributed in organs upon intravenous injection would be rapidly degraded and excreted without apparent in vivo toxicity. MoOx-PEG shows efficient accumulation in tumors, the acidic pH of which then leads to longer tumor retention of those nanosheets. Along with the capability of acting as a photothermal agent for effective tumor ablation, MoOx-PEG can load therapeutic molecules with high efficiencies. This concept of inorganic theranostic nanoagent should be relatively stable in tumors to allow imaging and treatment, while being readily degradable in normal organs to enable rapid excretion and avoid long-term retention/toxicity. [ABSTRACT FROM AUTHOR]

Molybdenum oxide (MoOx) nanosheets with high near-infrared (NIR) absorbance and pH-dependent oxidative degradation properties were synthesized, functionalized with polyethylene glycol (PEG), and then used as a degradable photothermal agent and drug carrier. The nanosheets, which are relatively stable under acidic pH, could be degraded at physiological pH. Therefore, MoOx-PEG distributed in organs upon intravenous injection would be rapidly degraded and excreted without apparent in vivo toxicity. MoOx-PEG shows efficient accumulation in tumors, the acidic pH of which then leads to longer tumor retention of those nanosheets. Along with the capability of acting as a photothermal agent for effective tumor ablation, MoOx-PEG can load therapeutic molecules with high efficiencies. This concept of inorganic theranostic nanoagent should be relatively stable in tumors to allow imaging and treatment, while being readily degradable in normal organs to enable rapid excretion and avoid long-term retention/toxicity. [ABSTRACT FROM AUTHOR]

Combining different therapeutic strategies to treat cancer by overcoming limitations of conventional cancer therapies has shown great promise in both fundamental and clinical studies. Herein, by adding 131I when making iodine-doped CuS nanoparticles, CuS/[131I]I nanoparticles are obtained, which after functionalization with polyethylene glycol (PEG) are used for radiotherapy (RT) and photothermal therapy (PTT), by utilizing their intrinsic high near-infrared absorbance and the doped 131I-radioactivity, respectively. The combined RT and PTT based on CuS/[131I]I-PEG is then conducted, achieving remarkable synergistic therapeutic effects as demonstrated in the treatment of subcutaneous tumors. In the meanwhile, as revealed by bimodal nuclear imaging and computed tomography (CT) imaging, it is found that CuS/[131I]I-PEG nanoparticles after being injected into primary solid tumors could migrate to and retain in their nearby sentinel lymph nodes. Importantly, the combined RT and PTT applied on those lymph nodes to assist surgical resection of primary tumors results in remarkably inhibited cancer metastasis and greatly prolonged animal survival. In vivo toxicology studies further reveal that our CuS/I-PEG is not obviously toxic to animals at fourfold of the treatment dose. This work thus demonstrates the potential of combining RT and PTT using a single nanoagent for imaging-guided treatment of metastatic tumors. [ABSTRACT FROM AUTHOR]

The development of cancer combination therapies, many of which rely on nanoscale theranostic agents, has received increasing attention in recent years. In this work, polyethylene glycol (PEG) modified mesoporous silica (MS) coated single-walled carbon nanotubes (SWNTs) are fabricated and utilized as a multifunctional platform for imaging guided combination therapy of cancer. A model chemotherapy drug, doxorubicin (DOX), could be loaded into the mesoporous structure of the obtained SWNT@MS-PEG nano-carriers with high efficiency. Upon stimulation under near-infrared (NIR) light, photothermally triggered drug release from DOX loaded SWNT@MS-PEG is observed inside cells, resulting in a synergistic cancer cell killing effect. As revealed by both photoacoustic (PA) and magnetic resonance (MR) imaging, we further uncover efficient tumor accumulation of SWNT@MS-PEG/DOX after intravenous injection into mice. In vivo combination therapy using this agent is further demonstrated in a mouse tumor model, achieving a remarkable synergistic anti-tumor effect superior to that obtained by mono-therapy. Our work presents a new type of theranostic nano-platform, which could load therapeutic molecules with high efficiency, be responsive to external NIR stimulation, and at the same time serve as a diagnostic imaging agent. [ABSTRACT FROM AUTHOR]

Photothermal therapy (PTT), as a minimally invasive and highly effective cancer treatment approach, has received widespread attention in recent years. Tremendous effort has been devoted to explore various types of photothermal agents with high near-infrared (NIR) absorbance for PTT cancer treatment. Despite many exciting progresses in the area, effective yet safe photothermal agents with good biocompatibility and biodegradability are still highly desired. In this work, a new organic PTT agent based on polyethylene glycol (PEG) coated micelle nanoparticles encapsulating a heptamethine indocyanine dye IR825 is developed, showing a strong NIR absorption band and a rather low quantum yield, for in vivo photothermal treatment of cancer. It is found that the IR825-PEG nanoparticles show ultra-high in vivo tumor uptake after intravenous injection, and appear to be an excellent PTT agent for tumor ablation under a low-power laser irradiation, without rendering any appreciable toxicity to the treated animals. Compared with inorganic nanomaterials and conjugated polymers being explored in PTT, the NIR-absorbing micelle nanoparticles presented here may have the least safety concern while showing excellent treatment efficacy, and thus may be a new photothermal agent potentially useful in clinical applications. [ABSTRACT FROM AUTHOR]

Recently, near-infrared (NIR) absorbing conjugated polymeric nanoparticles have received significant attention in photothermal therapy of cancer. Herein, polypyrrole (PPy), a NIR-absorbing conjugate polymer, is used to coat ultra-small iron oxide nanoparticles (IONPs), obtaining multifunctional IONP@PPy nanocomposite which is further modified by the biocompatible polyethylene glycol (PEG) through a layer-by-layer method to acquire high stability in physiological solutions. Utilizing the optical and magnetic properties of the yielded IONP@PPy-PEG nanoparticles, in vivo magnetic resonance (MR) and photoacoustic imaging of tumor-bearing mice are conducted, revealing strong tumor uptake of those nanoparticles after intravenous injection. In vivo photothermal therapy is then designed and carried out, achieving excellent tumor ablation therapeutic effect in mice experiments. These results promise the use of multifunctional NIR-absorbing organic-inorganic hybrid nanomaterials, such as IONP@PPy-PEG presented here, for potential applications in cancer theranostics. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) based on upconversion nanoparticles (UCNPs) can effectively destroy cancer cells under tissue-penetrating near-infrared light (NIR) light. Herein, we synthesize manganese (Mn2+)-doped UCNPs with strong red light emission at ca. 660 nm under 980 nm NIR excitation to activate Chlorin e6 (Ce6), producing singlet oxygen (1O2) to kill cancer cells. A layer-by-layer (LbL) self-assembly strategy is employed to load multiple layers of Ce6 conjugated polymers onto UCNPs via electrostatic interactions. UCNPs with two layers of Ce6 loading (UCNP@2xCe6) are found to be optimal in terms of Ce6 loading and 1O2 generation. By further coating UCNP@2xCe6 with an outer layer of charge-reversible polymer containing dimethylmaleic acid (DMMA) groups and polyethylene glycol (PEG) chains, we obtain a UCNP@2xCe6-DMMA-PEG nanocomplex, the surface of which is negatively charged and PEG coated under pH 7.4; this could be converted to have a positively charged naked surface at pH 6.8, significantly enhancing cell internalization of nanoparticles and increasing in vitro NIR-induced PDT efficacy. We then utilize the intrinsic optical and paramagnetic properties of Mn2+-doped UCNPs for in vivo dual modal imaging, and uncover an enhanced retention of UCNP@2xCe6-DMMA-PEG inside the tumor after intratumoral injection, owing to the slightly acidic tumor microenvironment. Consequently, a significantly improved in vivo PDT therapeutic effect is achieved using our charge-reversible UCNP@2xCe6-DMMA-PEG nanoparticles. Finally, we further demonstrate the remarkably enhanced tumor-homing of these pH-responsive charge-switchable nanoparticles in comparison to a control counterpart without pH sensitivity after systemic intravenous injection. Our results suggest that UCNPs with finely designed surface coatings could serve as smart pH-responsive PDT agents promising in cancer theranostics. [ABSTRACT FROM AUTHOR]

Efficient and safe gene transfection carriers, especially for hard-to-transfect cells, are urgently demanded in basic biological research and gene therapy applications. Many insect cell lines widely used in molecular cell biology exhibit relatively low transfection efficiencies when treated by conventional non-viral agents. Herein, we develop a novel gene delivery vector by coating graphene oxide (GO) with both polyethylene glycol (PEG) and polyethylenimine (PEI), obtaining a dual-polymer-functionalized nanoscale GO (nGO-PEG-PEI) to transfect insect cells. While exhibiting remarkably reduced cytotoxicity compared with PEI, nGO-PEG-PEI, when used as the plasmid DNA transfection agent to treat Drosophila S2 cells, offers ≈7-fold and ≈2.5-fold higher efficiency compared with those achieved by using bare PEI and Lipofectamine 2000, a widely used commercial transfection agent, respectively. Interestingly, the advantages of nGO-PEG-PEI are even more dramatic when transfecting cells with lower-quality linearized DNA. It is revealed that nGO-PEG-PEI/pDNA complexes enter insect cells via a unique pathway working even at a low temperature, rather different from their entry into mammalian adherent cells. Our results encourage the development of nano-GO-based gene carriers to treat special types of hard-to-transfect cells (e.g., insect cells), and indicate that nanomaterials would enter cells by cell-type-dependent mechanisms, which merit significantly more future attentions. [ABSTRACT FROM AUTHOR]

Effective and sustained tumor oxygenation has found practical significance in benefiting the treatment of solid tumors. In this study, fluorinated covalent organic polymers (COPs) are prepared by cross‐linking the photosensitizer meso‐5, 10, 15, 20‐tetra (4‐hydroxylphenyl) porphyrin (THPP) with perfluorosebacic acid (PFSEA) and poly(ethylene glycol) (PEG) via a one‐pot esterification, to enable simultaneous tumor oxygenation and photodynamic treatment. Due to the presence of PFSEA, the obtained THPPpf–PEG shows efficient loading of perfluoro‐15‐crown‐5‐ether (PFCE), a type of perfluocarbon, and thereby molecular oxygen, both of which would significantly enhance the photodynamic effect of THPP. After chelating THPP with a radio‐isotope, 99mTc, both THPPpf–PEG and PFCE‐loaded THPPpf–PEG (PFCE@THPPpf–PEG) can be vividly visualized under the single‐photon emission computed tomography (SPECT) imaging, which uncovers efficient tumor accumulation of those COPs' post intravenous injection. Owing to the oxygen delivery ability of PFCE, efficient tumor oxygenation is observed for mice post injection of PFCE@THPPpf–PEG, which further leads to greatly enhanced photodynamic treatment of tumors. This study presents a unique type of multifunctional fluorinated COPs with well‐defined composition, long blood circulation time, and sustained tumor oxygenation ability, showing great promises for potential clinical translation in photodynamic treatment of tumors. An intriguing type of fluorinated nanocovalent organic polymers, THPPpf–PEG, is prepared via a one‐pot esterification reaction and can work as an efficient shuttle of perfluorocarbon (PFC) and subsequent oxygen for sustained tumor hypoxia attenuation. Utilizing its effective photodynamic effect, such THPPpf–PEG with PFC loaded can contribute to greatly enhanced cancer photodynamic treatment upon laser exposure. [ABSTRACT FROM AUTHOR]