Cancer nutritional-immunotherapy with NIR-II laser-controlled ATP release based on material repurposing strategy.

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.

Injectable Magnetic Hydrogel Filler for Synergistic Bone Tumor Hyperthermia Chemotherapy.

The therapeutic efficacy of bone tumor treatment is primarily limited by inadequate tumor resection, resulting in recurrence and metastasis, as well as the deep location of tumors. Herein, an injectable doxorubicin (DOX)-loaded magnetic alginate hydrogel (DOX@MAH) was developed to evaluate the efficacy of an alternating magnetic field (AMF)-responsive, chemothermal synergistic therapy for multimodality treatment of bone tumors. The prepared hydrogel exhibits a superior drug-loading capacity and a continuous DOX release. This multifunctionality can be attributed to the combined use of DOX for chemotherapy and iron oxide nanoparticle-containing alginate hydrogels as magnetic hyperthermia agents to generate hyperthermia for tumor elimination without the limit on penetration depth. Moreover, the hydrogel can be formed when in contact with the calcium ions, which are abundant in bone tissues; therefore, this hydrogel could perfectly fit the bone defects caused by the surgical removal of the bone tumor tissue, and the hydrogel could tightly attach the surgical margin of the bone to realize a high efficacy residual tumor tissue elimination treated by chemothermal synergistic therapy. The hydrogel demonstrates excellent hyperthermia performance, as evidenced by in vitro cytotoxicity tests on tumor cells. These tests reveal that the combined therapy based on DOX@MAH under AMF significantly induces cell death compared to single magnetic hyperthermia or chemotherapy. In vivo antitumor effects in tumor-bearing mice demonstrate that DOX@MAH injection at the tumor site effectively inhibits tumor growth and leads to tumor necrosis. This work not only establishes an effective DOX@MAH system as a synergistic chemothermal therapy platform for treating bone tumors but also sheds light on the application of alginate to combine calcium ions of the bone to treat bone defect diseases.

Acidity-Triggered Charge-Convertible Conjugated Polymer for Dihydroartemisinin Delivery and Tumor-Specific Chemo-Photothermal Therapy.

Since the nonspecificity and nonselectivity of traditional treatment models lead to the difficulty of cancer treatment, nanobased strategies are needed to fill in the gaps of current approaches. Herein, a tumor microenvironment (TME)-responsive chemo-photothermal treatment model was developed based on dihydroartemisinin (DHA)-loaded conjugated polymers (DHA@PLGA-PANI). The synthesized DHA@PLGA-PANI exhibited enhanced photothermal properties under mild-acidic conditions and thus triggered local heat at the tumor site. Meanwhile, these iron-doped conjugated polymers of PLGA-PANI were used as the source of Fe, and benefiting from the Fe-dependent cytotoxicity of DHA, the burst of free radicals could be generated in tumors. Therefore, the combination of TME-responsive chemo-photothermal therapy could achieve effective tumor efficacy.

Hypoxia Alleviated and One Photo-Triggered Thermal/Dynamic Nanoplatform for Immunogenic Cell Death-Initiated Cancer Immunotherapy.

Immunogenic cell death (ICD) induced by treatment modalities like chemotherapy, radiotherapy, and photothermal and photodynamic therapy has shown great potential to improve the low response rate of various solid tumors in cancer immunotherapy. However, extensive studies have revealed that the efficacy of cancer treatment is limited by the hypoxia and immunosuppression in the tumor microenvironment (TME). To address these challenges, a hypoxia alleviated and one phototriggered thermal/dynamic nanoplatform based on MnO2@PDA/ICG-BSA (MPIB) is developed for oxygen (O2) self-supply enhanced cancer phototherapy (PT). First, MnO2 transfers intracellular overexpression H2O2 into O2 in the acidic TME through its catalase-like activity to improve the hypoxia and also provide O2 for the following photodynamic therapy. Then, under single NIR-808 nm light irradiation (called the "phototherapeutic window"), excellent photothermal and photodynamic performance of the MPIB is activated for combined PT. Finally, assisted with immune adjuvant cytosine-phospho-guanine, obvious ICD and systemic antitumor immunity was elicited in PT-treated mice and demonstrated significant growth inhibition on distant tumors. This MPIB-based nanoplatform highlights the promise to overcome the limitations of hypoxia and also challenges of immunosuppressive tumor microenvironments for improved cancer immunotherapy.

Boosting the photothermal performance of vacancy-rich MoSe2-x nanoflowers for photoacoustic imaging guided tumor chemo-photothermal therapy.

Due to the relatively low photo-thermal conversion efficiency and poor tumor targeting capacity, phototheranostic nanoagents encounter some challenges in cancer photothermal therapy. To address this problem, in the current research we developed vacancy-rich MoSe2-x (0 ≤ x ≤ 1) nanoflowers (MNFs) with molecular 2-deoxy-D-glucose (2-DG) as the activity target, which could be used as a novel phototheranostic nanoagent in the photoacoustic imaging guided chemo-photothermal synergistic therapy. This selenium-deficient structure endows MNFs with high photothermal conversion efficiency (41.7%) due to the strong localized surface plasmon resonances. Besides, the surface linked 2-DG molecules and the flower-like morphology in the nanoagents promoted the targeting effect (active and passive), thus facilitating the efficient concentration of the nanoagents within the tumor site. Both in vitro and in vivo anti-tumor experiments have demonstrated the high synergistic efficacy promoted by MNFs and complete tumor eradication with lower administration dosages could be achieved. This rational design of nanoparticles not only provided the paradigm of high therapeutic efficacy of a chemo-photothermal protocol for precise cancer theranostics, but also expanded the scope of nanomedical applications using semiconductor-based nanoplatforms through well-defined designing of their microstructures and physiochemical properties.

Hypoxia-Overcoming Breast-Conserving Treatment by Magnetothermodynamic Implant for a Localized Free-Radical Burst Combined with Hyperthermia.

For the purpose of improving the quality of life and minimizing the psychological morbidity of a mastectomy, breast-conserving treatment (BCT) has become the more preferable choice in breast cancer patients. Meanwhile, tumor hypoxia has been increasingly recognized as a major deleterious factor in cancer therapies. In the current study, a novel, effective, and noninvasive magnetothermodynamic strategy based on an oxygen-independent free-radical burst for hypoxia-overcoming BCT is proposed. Radical precursor (AIPH) and iron oxide nanoparticles (IONPs) are coincorporated within the alginate (ALG) hydrogel, which is formed in situ within the tumor tissue by leveraging the cross-linking effect induced by the local physiological Ca2+ with ALG solution. Inductive heating is mediated by IONPs under AMF exposure, and consequently, regardless of the tumor hypoxia condition, a local free-radical burst is achieved by thermal decomposition of AIPH via AMF responsivity. The combination of magnetic hyperthermia and oxygen-irrelevant free-radical production effectively enhances the in vitro cytotoxic effect and also remarkably inhibits tumor proliferation. This study provides a valuable protocol for an hypoxia-overcoming strategy and also an alternative formulation candidate for noninvasive BCT.

A Scoping Review of Cross-Sectional Studies on Traditional Chinese Medicine.

Cross-sectional studies on traditional Chinese medicine (TCM-CSs) have become the most published type of TCM observational study; however, the research scope of current TCM-CSs is unknown. A scoping review of the literature was performed. A descriptive approach to summarize the core study characteristics was prepared, along with structured tables and figures to identify salient points of similarities and differences noted across studies. The reporting quality of TCM-CSs was assessed according to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) cross-sectional checklist. Eight databases (Embase, CENTRAL, MEDLINE, AMED, CBM, CNKI, WanFang, and VIP) were systematically searched for TCM-CSs published up until 20 January 2020. The literature screening and evaluating were independently conducted by two researchers. When there was disagreement, a third-party senior researcher made the judgment. A total of 198 TCM-CSs published between 1997 and 2019 were included, 160 English studies and 38 Chinese studies, respectively. More TCM-CSs were published in each successive year. The journal Evidence-Based Complementary and Alternative Medicine published more TCM-CSs (24) than any other journal. Most TCM-CSs were conducted in mainland China (81, 40.9%), followed by Taiwan, China (44, 22.2%) and HKSAR, China (19, 9.6%). The most commonly used sampling method was purposive sampling (94, 47.5%), following by convenience sampling (60, 30.3%). The research topics can be summarized in four major categories as follows: constitution-related research (11.1%), TCM pattern-related research (18.7%), TCM intervention-related research (55.1%), and others (15.6%). The average sufficient reporting rate of included TCM-CSs according to the STROBE cross-sectional checklist was 45.6%. Papers written in English reported 9 items (items 2, 4, 14a, 16a, 18, 19, 20, 21, and 22) more frequently than papers written in Chinese. The number of TCM-CSs is increasing. Research topics are diverse; however, the reporting quality is unsatisfactory. In particular, TCM-CSs need greater transparency and standardization.

Ferrous ions doped layered double hydroxide: smart 2D nanotheranostic platform with imaging-guided synergistic chemo/photothermal therapy for breast cancer.

Developing simple and efficient nanotheranostic platforms with behavior responsive to the acid microenvironment of a tumor is of great significance for accurate tumor diagnosis and therapy. In this study, a smart 2D nanotheranostic platform has been successfully fabricated by doping functional ferrous ions into as-synthesized MgAl-layered double hydroxide (LDH) with doxurubicin (DOX) loading to form Fe-LDH/DOX NPs, which achieved magnetic resonance imaging (MRI)-guided synergistic chemo/photothermal therapy for breast cancer. The doping of ferrous ions into Fe-LDH/DOX enabled a strong photo-induced heating ability with a high photothermal conversion efficiency of 45.67%, which could be combined with the antitumor drug DOX to achieve the synergistic effect of photothermal therapy (PTT) and chemotherapy for killing tumor cells. Additionally, its in vitro pH-dependent degradation behavior and T2-weighted MRI effect revealed that the as-prepared Fe-LDH/DOX is sensitive to the tumor acid microenvironment. Most importantly, the growth rate of tumors in 4T1 bearing mice could be effectively inhibited after the synergistic treatment of PTT and chemotherapy by Fe-LDH/DOX. These results show that doping functional metal ions into LDH NPs may open a novel approach to fabricating an LDH NP-based nanotheranostics platform with advanced diagnostic and therapeutic performances.

Ferrimagnetic Vortex Nanoring-Mediated Mild Magnetic Hyperthermia Imparts Potent Immunological Effect for Treating Cancer Metastasis.

Cancer metastasis is a serious concern and a major reason for treatment failure. Herein, we have reported the development of an effective and safe nanotherapeutic strategy that can eradicate primary tumors, inhibit metastasizing to lung, and control the metastasis and growth of distant tumors. Briefly, ferrimagnetic vortex-domain iron oxide nanoring (FVIO)-mediated mild magnetic hyperthermia caused calreticulin (CRT) expression on the 4T1 breast cancer cells. The CRT expression transmitted an "eat-me" signal and promoted phagocytic uptake of cancer cells by the immune system to induce an efficient immunogenic cell death, further leading to the macrophage polarization. This mild thermotherapy promoted 88% increase of CD8+ cytotoxic T lymphocyte infiltration in distant tumors and triggered immunotherapy by effectively sensitizing tumors to the PD-L1 checkpoint blockade. The percentage of CD8+ cytotoxic T lymphocytes can be further increased from 55.4% to 64.5% after combining with PD-L1 blockade. Moreover, the combination treatment also inhibited the immunosuppressive response of the tumor, evidenced by significant down-regulation of myeloid-derived suppressor cells (MDSCs). Our results revealed that the FVIO-mediated mild magnetic hyperthermia can activate the host immune systems and efficiently cooperate with PD-L1 blockade to inhibit the potential metastatic spreading as well as the growth of distant tumors.

Non-Magnetic Injectable Implant for Magnetic Field-Driven Thermochemotherapy and Dual Stimuli-Responsive Drug Delivery: Transformable Liquid Metal Hybrid Platform for Cancer Theranostics.

Transformable liquid metal (LM)-based materials have attracted considerable research interest in biomedicine. However, the potential biomedical applications of LMs have not yet been fully explored. Herein, for the first trial, the inductive heating property of gallium-indium eutectic alloy (EGaIn) under alterative magnetic field is systematically investigated. By virtue of its inherent metallic nature, LM possesses excellent magnetic heating property as compared to the conventional magnetite nanoparticles, therefore enabling its unique application as non-magnetic agents in magnetic hyperthermia. Moreover, the extremely high surface tension of LM could be dramatically lowered by a rather facile PEGylation approach, making LM an ideal carrier for other theranostic cargos. By incorporating doxorubicin (DOX)-loaded mesoporous silica (DOX-MS) within PEGylated LM, a magnetic field-driven transformable LM hybrid platform capable of pH/AFM dual stimuli-responsive drug release and magnetic thermochemotherapy are successfully fabricated. The potential application for breast cancer treatment is demonstrated. Furthermore, the large X-ray attenuation ability of LM endows the hybrid with the promising ability for CT imaging. This work explores a new biomedical use of LM and a promising cancer treatment protocol based on LM hybrid for magnetic hyperthermia combined with dual stimuli-responsive chemotherapy and CT imaging.

Nonmagnetic Hypertonic Saline-Based Implant for Breast Cancer Postsurgical Recurrence Prevention by Magnetic Field/pH-Driven Thermochemotherapy.

Magnetic-mediated hyperthermia (MMT) is emerging as one of the promising techniques, which could synergistically treat cancer along with current treatment techniques such as chemotherapy and radiotherapy and trigger on-demand release of therapeutic macromolecules. However, the low specific absorption rate and potential in vivo toxicity of magnetic nanomaterials as the MMT mediators restrict the new advancements in MMT treatment. Herein, for the first trial, the unique inductive heating property of hypertonic saline (HTS), a clinically applied solution exhibiting several physiological effects under alternative magnetic field (AMF), was systematically investigated. Though without magnetic property, due to the dipolar polarization under the electromagnetic radiation, HTS can induce enough high and rapid temperature increase upon exposure under AMF. Based on such an observation, PEG-based HTS hydrogel was fabricated for the inhibition of unwanted diffusion of ions so as to ensure the ideal temperature rise at the targeted region for a longer time. Furthermore, an anticancer drug (doxorubicin) was also incorporated into the hydrogel to achieve the magnetic field/pH stimuli-responsive drug-sustainable release as well as synergistic thermochemotherapy. The potential application of the drug-loaded HTS-PEG-injectable hydrogel for breast cancer postsurgical recurrence prevention is demonstrated. Significant in vivo suppression of two kinds of breast cancer models was achieved by the hybrid hydrogel system. This work explores a new biomedical use of clinical HTS and a promising cancer treatment protocol based on HTS-PEG hydrogel for magnetic hyperthermia combined with stimuli-responsive chemotherapy for breast cancer postsurgical recurrence prevention.

Neoadjuvant nano-photothermal therapy used before operation effectively assists in surgery for breast cancer.

Nano-photothermal therapy (NPTT) has attracted increasing interest recently due to its high efficiency, excellent selectivity and non-ionizing radiation damage. Despite a tremendous amount of exciting pre-clinical results reported in the past few years, however, the further clinic application of NPTT is still difficult. To combine NPTT with clinical surgery more closely, novel multifunctional optical-magnetic nanosystems have been synthesized and applied for preoperative NPTT to assist in the follow-up surgery, termed "neoadjuvant NPTT". Remarkably, nanoparticles are mainly aggregated in the cytoplasm of tumor cells in vitro and largely accumulated in the tumor in vivo 24 h after injection. Under the guidance of tri-modality imaging, preoperative NPTT could shrink the tumor in a short time and make the boundary between the tumor and surrounding normal tissues clearer, which is conducive to subsequent surgery resection. Furthermore, the 50% survival rate is up to 50 days compared with 35 days for standard surgery, 31 days for PTT alone and 24 days for non-surgery groups. Therefore, NPTT can effectively assist in surgery used before operation. This study provides a new idea for the clinical transformation of NPTT in the future.

Amid proton transfer (APT) and magnetization transfer (MT) MRI contrasts provide complimentary assessment of brain tumors similarly to proton magnetic resonance spectroscopy imaging (MRSI).

OBJECTIVES: Using MRSI as comparison, we aimed to explore the difference between amide proton transfer (APT) MRI and conventional semi-solid magnetization transfer ratio (MTR) MRI, and to investigate if molecular APT and structural MTR can provide complimentary information in assessing brain tumors. METHODS: Seventeen brain tumor patients and 17 age- and gender-matched volunteers were included and scanned with anatomical MRI, APT and MT-weighted MRI, and MRSI. Multi-voxel choline (Cho) and N-acetylaspartic acid (NAA) signals were quantified from MRSI and compared with MTR and MTRasym(3.5ppm) contrasts averaged from corresponding voxels. Correlations between contrasts were explored voxel-by-voxel by pooling values from all voxels into Pearson's correlation analysis. Differences in correlation coefficients were tested with the Z-test (set at p<0.05). RESULTS: APT and MT provide good contrast and quantitative parameters in tumor imaging, as do the metabolite (Cho and NAA) maps. MTRasym(3.5ppm) significantly correlated with MTR (R=-0.61, p<0.0001), Cho (R=0.568, p<0.0001) and NAA (R=-0.619, p<0.0001) in tumors, and MTR also significantly correlated with Cho (R=-0.346, p<0.0001) and NAA (R=0.624, p<0.0001). In healthy volunteers, MTRasym(3.5ppm) was non-significantly correlated with MTR (R=-0.049, p=0.239), Cho (R=0.030, p=0.478) and NAA (R=-0.083, p=0.046). Significant correlations were found among MTR with Cho (R=0.199, p<0.0001) and NAA (R=0.263, p<0.0001) in the group of healthy volunteers with lower correlation R values than those in tumor patients. CONCLUSIONS: APT and MT could provide independent and supplementary information for the comprehensive assessment of molecular and structural changes due to brain tumor cancerogenesis. KEY POINTS: • MTR asym(3.5ppm) positively correlated with Cho while negatively with NAA in tumors. • MTR positively correlated with NAA while negatively with Cho in tumors. • Combining APT/MT provides molecular and structural information similarly to MRSI.

Effect of nanoheat stimulation mediated by magnetic nanocomposite hydrogel on the osteogenic differentiation of mesenchymal stem cells.

Hyperthermia has been considered as a promising healing treatment in bone regeneration. We designed a tissue engineering hydrogel based on magnetic nanoparticles to explore the characteristics of hyperthermia for osteogenic regeneration. This nanocomposite hydrogel was successfully fabricated by incorporating magnetic Fe3O4 nanoparticles into chitosan/polyethylene glycol (PEG) hydrogel, which showed excellent biocompatibility and were able to easily achieve increasing temperatures under an alternative magnetic field (AMF). With uniformly dispersed nanoparticles, the composite hydrogel resulted in high viability of mesenchymal stem cells (MSCs), and the elevated temperature contributed to the highest osteogenic differentiation ability compared with direct heat treatment applied under equal temperatures. Therefore, the nanoheat stimulation method using the magnetic nanocomposite hydrogel under an AMF may be considered as an alternative candidate in bone tissue engineering regenerative applications.

Drug-Loaded Magnetic Microhydrogel as Microwave Susceptible Agents for Cancer Multimodality Treatment and MR Imaging.

Microwave (MW) ablation has been widely recognized as one of prominent protocols for clinical cancer treatment with advantages of minimally invasive treatment, convenient operation and consistent intra-tumoral temperature. However, microwave therapeutic approach still has the risk of overheating the surrounding healthy tissues, which thus necessitates susceptible agent to concentrate the heat and enhance the treatment efficiency with lower microwave power while avoiding side effects. Herein, a doxorubicin (DOX)-loaded magnetic nanocomposite calcium alginate microhydrogel (Fe3O4@DOX/CAM) as microwave susceptible and MR contrast agent has been developed for in vivo tumor multimodality therapy. Membrane emulsification method was employed for the fabrication of the monodispersed microhydrogel with rather uniform size distribution. Even under microwave irradiation at extremely low microwave power (2 W), enough heat (∼50 °C) can be induced by the microhydrogel. Except for as an excellent susceptible agent for microwave thermotherapy, the as-prepared Fe3O4@DOX/CAM can achieve microwave responsive DOX delivery, as it was noticed that microwave heating can actually facilitate drug release. Moreover, such multifunctional Fe3O4@DOX/CAM can be administered by intra-tumoral injection to achieve MW thermotherapy combined with sustainable chemotherapy. Meanwhile, the magnetic nanoparticles incorporated within the microhydrogel can be applied for T2-weighted MR image during the cancer treatment. In summary, our observations on such Fe3O4@DOX/CAM suggest an effective microwave susceptible agent for cancer multimodality treatment and imaging.

Melatonin potentiates "inside-out" nano-thermotherapy in human breast cancer cells: a potential cancer target multimodality treatment based on melatonin-loaded nanocomposite particles.

PURPOSE: With the wide recognition of oncostatic effect of melatonin, the current study proposes a potential breast cancer target multimodality treatment based on melatonin-loaded magnetic nanocomposite particles (Melatonin-MNPs). METHODS: Melatonin-MNPs were fabricated by the single emulsion solvent extraction/evaporation method. RESULTS: Based on the facilitated transport of melatonin by the GLUT overexpressed on the cell membrane, such Melatonin-MNPs can be more favorably uptaken by MCF-7 cells compared with the melatonin-free nanocomposite particles, which indicates the cancer targeting ability of melatonin molecule. Inductive heating can be generated by exposure to the Melatonin-MNPs internalized within cancer cells under alternative magnetic field, so as to achieve the "inside-out" magnetic nano-thermotherapy. In addition to demonstrating the superior cytotoxic effect of such nano-thermotherapy over the conventional exogenous heating by metal bath, more importantly, the sustainable release of melatonin from the Melatonin-MNPs can be greatly promoted upon responsive to the magnetic heating. The multimodality treatment based on Melatonin-MNPs can lead to more significant decrease in cell viability than any single treatment, suggesting the potentiated effect of melatonin on the cytotoxic response to nano-thermotherapy. CONCLUSION: This study is the first to fabricate the precisely engineered melatonin-loaded multifunctional nanocomposite particles and demonstrate the potential in breast cancer target multimodality treatment.

Photoinduced Mild Hyperthermia and Synergistic Chemotherapy by One-Pot-Synthesized Docetaxel-Loaded Poly(lactic-co-glycolic acid)/Polypyrrole Nanocomposites.

Mild hyperthermia has shown great advantages when combined with chemotherapy. The development of a multifunctional platform for the integration of mild hyperthermia capability into a drug-loading system is a key issue for cancer multimodality treatment application. Herein, a facile one-pot in situ fabrication protocol of docetaxel (DTX)-loaded poly(lactic-co-glycolic acid) (PLGA)/polypyrrole (PPy) nanocomposites was developed. While the PLGA nanoparticles (NPs) allow efficient drug loading, the PPy nanobulges embedded within the surface of the PLGA NPs, formed by in situ pyrrole polymerization without the introduction of other template agents, can act as ideal mediators for photoinduced mild hyperthermia. Physiochemical characterizations of the as-prepared nanocomposites, including structure, morphology, photothermal effects, and an in vitro drug release profile, were systematically investigated. Further, 2-deoxyglucose-terminated poly(ethylene glycol) (PEG) was anchored onto the surface of the nanocomposites to endow the nanoplatform with targeting ability to tumor cells, which resulted in a 17-fold increase of NP internalization within human breast cancer cells (MCF-7) as competed with PEG-modified nanocomposites. Mild hyperthermia can be successfully mediated by the nanoplatform, and the temperature can be conveniently controlled by careful modulation of the PPy contents within the nanocomposites or the laser power density. Importantly, we have demonstrated that MCF-7 cells, which are markedly resistant to heat treatment of traditional water-bath hyperthermia, became sensitive to the PLGA/PPy nanocomposite-mediated photothermal therapy under the same mild-temperature hyperthermia. Moreover, DTX-loaded PLGA/PPy-nanocomposite-induced mild hyperthermia can strongly enhance drug cytotoxicity to MCF-7 cells. Under the same thermal dose, photoinduced hyperthermia can convert the interaction between hyperthermia and drug treatment from interference to synergism. This is the first report on the one-pot synthesis of PLGA/PPy nanocomposites by in situ pyrrole polymerization, and such a multifunctional nanoplatform is demonstrated as a high-potential agent for photoinduced mild hyperthermia and enhanced chemotherapy.

2-Deoxy-D-Glucose Modified Magnetic Nanoparticles with Dual Functional Properties: Nanothermotherapy and Magnetic Resonance Imaging.

Superparamagnetic iron oxide nanoparticles (SPIONs) with appropriate surface chemistry have attracted wild attention in medical and biological application because of their current and potential usefulness such as magnetic resonance imaging (MRI) contrast enhancement, magnetic mediated hyperthermia (MMH), immunoassay, and in drug delivery, etc. In this study, we investigated the MRI contrast agents and MMH mediators properties of the novel 2-deoxy-D-glucose (2-DG) modified SPIONs. As a non-metabolizable glucose analogue, 2-DG can block glycolysis and inhibits protein glycosylation. Moreover, SPIONs coated with 2-DG molecules can be particularly attractive to resource-hungry cancer cells, therefore to realize the targeting strategy for the SPIONs. SPIONs with amino silane as the capping agent for amino-group surface modification were synthesized by the chemical co-precipitation method with modification. Glutaraldehyde was further applied as an activation agent through which 2-DG was conjugated to the amino-coated SPIONs. Physicochemical characterizations of the 2-DG-SPIONs, such as surface morphology, surface charge and magnetic properties were investigated by Transmission Electron Microscopy (TEM), ζ-Potential and Vibrating Sample Magnetometer (VSM), etc. Magnetic inductive heating characteristics of the 2-DG-SPIONs were analyzed by exposing the SPIONs suspension (magnetic fluid) under alternative magnetic field (AMF). U-251 human glioma cells with expression of glucose transport proteins type 1 and 3 (GLUT1 and GLUT 3), and L929 murine fibroblast cell as negative control, were employed to study the effect of 2-DG modification on the cell uptake for SPIONs. TEM images for ultra-thin sections as well as ICP-MS were applied to evaluate the SPIONs internalization within the cells. In vitro MRI was performed after cells were co-incubated with SPIONs and the T2 relaxation time was measured and compared. The results demonstrate that 2-DG-SPIONs were supermagnetic and in spherical shape with -10 nm diameter. Possessing ideal magnetic inductive heating characteristics, which can generate very rapid and efficient heating while upon AMF exposure, 2-DG-SPIONs can be applied as novel candidature of magnetic nanothermotherapy for cancer treatment. Modification of 2-DG can greatly promote the cell uptake of SPIONs and such cellular uptake of 2-DG-SPIONs was time dependent. Surface coating by 2-DG can remarkably enhance the MR imaging ability for the SPIONs on the cells of U251 cancer cells. In summary, our investigation provides a novel glucose analogue modified SPIONs with potential application in the targeting cancer nanothermotherapy and MR imaging.

Multifunctional Fe5 C2 nanoparticles: a targeted theranostic platform for magnetic resonance imaging and photoacoustic tomography-guided photothermal therapy.

Fe5 C2 NPs exhibit a high contrast in magnetic resonance imaging (MRI), superior photoacoustic tomography improvements, and efficient photothermal therapy (PTT) due to their unique core/shell structure, with a magnetic core and carbon shell. By conjugating a new class of affinity proteins (ZHER2:342), they can target to tumor cells with low cytotoxicity, and kill them through laser irritation. It is also possible to ablate tumors under guidance by MRI and PTT without noticeable side effects.

Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia.

Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment.