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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]

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]

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]

Abstract: Mesenchymal stem cells (MSCs) have shown great potential in regenerative medicine. Sensitive and reliable methods for stem cell labeling and in vivo tracking are thus of great importance. Herein, we report the use of upconversion nanoparticles (UCNPs) as an exogenous contrast agent to track mouse MSCs (mMSCs) in vivo. To improve the labeling efficiency, oligo-arginine is conjugated to polyethylene glycol (PEG) coated UCNPs to enhance the nanoparticles uptake by mMSCs. Systematic in vitro tests reveal that the proliferation and differentiation of mMSCs are not notably affected by UCNP-labeling, suggesting that the labeled cells are able to maintain their stem cell potency. No apparent exocytosis is found in our in vitro labeling experiment by using a transwell culture system over a course of 10 days, indicating the potential capability of using our UCNP-labeling method for long-term stem cell tracking. To demonstrate the tracking sensitivity of our stem cell labeling approach, UCNP-labeled mMSCs are subcutaneously transplanted into mice and imaged using an in vivo upconversion luminescence (UCL) imaging system. As few as ∼10 cells labeled with UCNPs are detected in vivo, evidencing a remarkable improvement in detection sensitivity of our UCNP-labeled hMSCs compared with other stem cell labeling techniques using conventional exogenous agents. We further track UCNP-labeled mMSCs after intravenous injection, and observe the translocation of mMSCs from lung where they initially accumulate, to liver, a phenomenon consistent to previous reports. Our results highlight the promise of using UCNPs as a new type of ultra-sensitive probes for labeling and in vivo tracking of stem cells at nearly the single cell level. [Copyright &y& Elsevier]

Overexpression of P-glycoprotein (P-gp), which is responsible for pumping chemotherapeutic drugs out of tumor cells, has been recognized as an important cause of drug resistance in conventional chemotherapy. Herein, porous platinum nanoparticles (pPt NPs) are developed to enable the combined electrodynamic therapy (EDT) with chemotherapy. With polyethylene glycol (PEG) coating, the obtained pPt-PEG NPs could be loaded with anticancer drug doxorubicin (DOX) by utilizing the porous structure of pPt NPs. Those pPt-PEG NPs are able to produce reactive oxygen species (ROS) by triggering water decomposition under electric field, independent of O 2 and H 2 O 2 contents in the tumor. Furthermore, the ROS generated during EDT could induce the inhibition of P-glycoprotein (P-gp), in turn enhancing the efficacy of chemotherapeutic agents by facilitating intracellular accumulation of drugs. As the results, excellent synergetic therapeutic effects were observed by combining chemotherapy with EDT using DOX-loaded pPt (DOX@pPt-PEG) NPs, as demonstrated by both in vitro and in vivo experiments. This study demonstrates a new concept of combinational cancer therapy with superior therapeutic efficacy. [ABSTRACT FROM AUTHOR]