Search

Abstract: Upconversion nanoparticles (UCNPs) with unique multi-photon excitation photoluminescence properties have recently been intensively explored as novel contrast agents for low-backgroundbiomedical imaging. In this work, we functionalize UCNPs with a polyethylene glycol (PEG) grafted amphiphilic polymer. The PEGylated UCNPs are loaded with a commonly used chemotherapy molecule, doxorubicin (DOX), by simple physical adsorption via a supramolecular chemistry approach for intracellular drug delivery. The loading and releasing of DOX from UCNPs are controlled by varying pH, with an increased drug dissociation rate in acidic environment, favorable for controlled drug release. Upconversion luminescence (UCL) imaging by a modified laser scanning confocal microscope reveals the time course of intracellular delivery of DOX by UCNPs. It is found that DOX is shuttled into cells by the UCNP nano carrier and released inside cells after endocytosis. By conjugating nanoparticles with folic acid, which targets folate receptors over expressed on various types of cancer cells, we further demonstrate targeted drug delivery and UCL cell imaging with UCNPs. Besides DOX, this non-covalent drug loading strategy can also be used for loading of photosensitizer molecules on UCNPs for potential near-infrared light induced photodynamic therapy. Our results suggest the promise of UCNPs as interesting nano carriers for multi-functional cancer therapy and imaging. [ABSTRACT FROM AUTHOR]

Nanoscale coordination polymers (NCPs) are promising nanomedicine platforms featured with biodegradability and versatile functionalities. However, multi-step post-synthesis surface modification is usually required to functionalize as-made NCPs before their biomedical applications. Moreover, efforts are still required to design therapeutic NCPs responsive to the unique tumor microenvironment to achieve more specific and effective therapy. Herein, we uncover a simple yet general strategy to synthesize a series of polyethylene glycol (PEG) modified NCPs via a one-step method by adding poly-histidine-PEG co-polymer into the mixture of metal ions and organic ligands during NCPs formation. With NCPs consisting Ca 2+ /dicarboxylic cisplatin (IV) prodrug as the example, we show that such Ca/Pt(IV)@pHis-PEG NCPs are highly sensitive to pH changes. With slightly negative charges and compact structure under pH 7.4 during blood circulation, those NCPs exhibit efficient passive accumulation in the tumor, in which the reduced pH (c.a. 6.5) would trigger charge conversion and size expansion to enhance their tumor retention and cell internationalization. After cellular uptake, NCPs within cell endo-/lysosomes with further reduced pH would then lead to decomposition of those NCPs and thus drug release. Chemotherapy with Ca/Pt(IV)@pHis-PEG NCPs in our animal tumor model demonstrates great efficacy under low drug doses, and is found to be particularly effective towards solid tumors with reduced pH. [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]

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]

Abstract: Photothermal therapy as a physical treatment approach to destruct cancer has emerged as an alternative of currently used cancer therapies. Previously we have shown that polyethylene glycol (PEG) functionalized nano-graphene oxide (nGO-PEG) with strong optical absorption in the near-infrared (NIR) region was a powerful photothermal agent for in vivo cancer treatment. In this work, by using ultra-small reduced graphene oxide (nRGO) with non-covalent PEG coating, we study how sizes and surface chemistry affect the in vivo behaviors of graphene, and remarkably improve the performance of graphene-based in vivo photothermal cancer treatment. Owing to the enhanced NIR absorbance and highly efficient tumor passive targeting of nRGO-PEG, excellent in vivo treatment efficacy with 100% of tumor elimination is observed after intravenous injection of nRGO-PEG and the followed 808 nm laser irradiation, the power density (0.15 W/cm2, 5 min) of which is an order of magnitude lower than that usually applied for in vivo tumor ablation using many other nanomaterials. All mice after treatment survive over a period of 100 days without a single death or any obvious sign of side effect. Our results highlight that both surface chemistry and sizes are critical to the in vivo performance of graphene, and show the promise of using optimized nano-graphene for ultra-effective photothermal treatment, which may potentially be combined with other therapeutic approaches to assist our fight against cancer. [Copyright &y& Elsevier]

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]