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1.
J Med Case Rep ; 15(1): 16, 2021 Jan 20.
Article in English | MEDLINE | ID: mdl-33468218

ABSTRACT

BACKGROUND: Use of perfluorocarbon liquid (PFCL) has been increasingly growing as an adjuvant in vitreo-retina surgeries. Some commonly encountered complications with its use include subretinal migration, formation of sticky silicone oil or retained PFCL in vitreous cavity and anterior chamber. Scleral rupture during PFCL injection has a rare occurrence. We report an unexpected event of scleral rupture during PFCL injection and discuss the management challenges faced by the surgeon. CASE PRESENTATION: A 66 year indo-aryan male was undergoing pars-plana vitrectomy (PPV) with diagnosis of subtotal rhegmatogenous retinal detachment (RD) with Proliferative Vitreo-retonipathy (PVR)-B. After near total vitrectomy PFCL was being injected and then there was sudden poor visualization of fundus with development of bullous RD and globe hypotony. The surgeon was not able to figure out the cause of hypotony and air was switched on in the infusion cannula. This further complicated the situation resulting in migration of air in the anterior chamber, posterior dislocation of intraocular lens complex, 180° inferior retinal dialysis and ballooning of the conjunctiva which gave a clue of probable scleral rupture. Conjunctival peritomy was performed superiorly and scleral defect was noted. Intraocular tissue incarceration and air leak was visible from the wound. This confirmed scleral rupture during PFCL injection. Repositioning of incarcerated retina was not possible and retinectomy was performed followed by repair of scleral rupture with lots of difficulty in a vitrectomised eye. CONCLUSION: PFCL injection, a crucial step of vitreoretina surgery, should be performed slowly with extreme caution maintaining an optimal intraocular pressure to prevent devastating complications like scleral rupture.


Subject(s)
Fluorocarbons/administration & dosage , Intraoperative Complications/etiology , Intravitreal Injections/adverse effects , Retinal Detachment/surgery , Rupture/etiology , Sclera/injuries , Vitrectomy/methods , Vitreoretinopathy, Proliferative/surgery , Aged , Eye Injuries/etiology , Humans , Male , Vitreoretinal Surgery/methods
2.
Theranostics ; 10(17): 7510-7526, 2020.
Article in English | MEDLINE | ID: mdl-32685002

ABSTRACT

Tumor-associated macrophages (TAMs) enhance tumor growth in mice and are correlated with a worse prognosis for breast cancer patients. While early therapies sought to deplete all macrophages, current therapeutics aim to reprogram pro-tumor macrophages (M2) and preserve those necessary for anti-tumor immune responses (M1). Recent studies have shown that c-MYC (MYC) is induced in M2 macrophages in vitro and in vivo where it regulates the expression of tumor-promoting genes. In a myeloid lineage MYC KO mouse model, MYC had important roles in macrophage maturation and function leading to reduced tumor growth. We therefore hypothesized that targeted delivery of a MYC inhibitor to established M2 TAMs could reduce polarization toward an M2 phenotype in breast cancer models. Methods: In this study, we developed a MYC inhibitor prodrug (MI3-PD) for encapsulation within perfluorocarbon nanoparticles, which can deliver drugs directly to the cytosol of the target cell through a phagocytosis independent mechanism. We have previously shown that M2-like TAMs express significant levels of the vitronectin receptor, integrin ß3, and in vivo targeting and therapeutic potential was evaluated using αvß3 integrin targeted rhodamine-labeled nanoparticles (NP) or integrin αvß3-MI3-PD nanoparticles. Results: We observed that rhodamine, delivered by αvß3-rhodamine NP, was incorporated into M2 tumor promoting macrophages through both phagocytosis-independent and dependent mechanisms, while NP uptake in tumor suppressing M1 macrophages was almost exclusively through phagocytosis. In a mouse model of breast cancer (4T1-GFP-FL), M2-like TAMs were significantly reduced with αvß3-MI3-PD NP treatment. To validate this effect was independent of drug delivery to tumor cells and was specific to the MYC inhibitor, mice with integrin ß3 knock out tumors (PyMT-Bo1 ß3KO) were treated with αvß3-NP or αvß3-MI3-PD NP. M2 macrophages were significantly reduced with αvß3-MI3-PD nanoparticle therapy but not αvß3-NP treatment. Conclusion: These data suggest αvß3-NP-mediated drug delivery of a c-MYC inhibitor can reduce protumor M2-like macrophages while preserving antitumor M1-like macrophages in breast cancer.


Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Macrophages/drug effects , Nanoparticles/administration & dosage , Proto-Oncogene Proteins c-myc/antagonists & inhibitors , Animals , Antineoplastic Agents/chemistry , Breast Neoplasms/pathology , Carcinogenesis/drug effects , Carcinogenesis/immunology , Cell Line, Tumor/transplantation , Drug Evaluation, Preclinical , Female , Fluorocarbons/administration & dosage , Fluorocarbons/chemistry , Gene Knockout Techniques , Humans , Integrin alphaVbeta3 , Integrin beta3 , Macrophages/immunology , Macrophages/metabolism , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/pathology , Mice , Nanoparticles/chemistry , Phagocytosis , Primary Cell Culture , Prodrugs/administration & dosage , Proto-Oncogene Proteins c-myc/metabolism , Tumor Microenvironment/drug effects , Tumor Microenvironment/immunology
3.
Chem Res Toxicol ; 33(7): 1605-1608, 2020 07 20.
Article in English | MEDLINE | ID: mdl-32372641

ABSTRACT

The present study exposed adult zebrafish to 0, 10, and 100 µg/L perfluorobutanesulfonate (PFBS) with or without dietary supplement of probiotic Lactobacillus rhamnosus. Interaction between probiotic and PFBS on sex endocrine and reproduction was investigated. It was striking to find that PFBS and probiotic coexposures almost ceased the fecundity, which was accompanied by disturbances in sex hormones and oocyte maturation in females. In contrast, probiotic additive efficiently antagonized the estrogenic activity of PFBS in males. For the first time, this study reported that probiotic heavily depended on sex to modulate the endocrine disruption and reproductive toxicity of aquatic pollutants.


Subject(s)
Endocrine Disruptors/toxicity , Fluorocarbons/toxicity , Probiotics/toxicity , Reproduction/drug effects , Sulfonic Acids/toxicity , Water Pollutants, Chemical/toxicity , Animals , Dietary Supplements , Endocrine Disruptors/administration & dosage , Estrogens/metabolism , Female , Fluorocarbons/administration & dosage , Gonadal Steroid Hormones/antagonists & inhibitors , Lacticaseibacillus rhamnosus/chemistry , Male , Oocytes/drug effects , Probiotics/administration & dosage , Sulfonic Acids/administration & dosage , Water Pollutants, Chemical/administration & dosage , Zebrafish
4.
Biomater Sci ; 8(9): 2488-2506, 2020 May 06.
Article in English | MEDLINE | ID: mdl-32211626

ABSTRACT

Theranostics is a new trend integrating diagnostic and therapeutic functions in tumour research. Theranostic nanoparticles enabling both tumour imaging and drug delivery are a promising platform for image-guided cancer therapy. Photodynamic therapy (PDT) has great potential in synergy with traditional chemotherapy but faces great challenges due to hypoxia, poor targeting ability and the limited penetration depth of visible light. To solve these problems, we presented a novel nanosystem of FA/UCNPs-RB/HCPT/PFH@lipid (denoted as FURH-PFH-NPs), with a perfluorohexane (PFH) carrying rich oxygen core and a folic acid-modified lipid shell. The shell contains 10-hydroxycamptothecin (HCPT) and self-fluorescing photosensitizer compounds, namely, upconversion nanoparticles and rose bengal (UCNPs-RB). In this study, FURH-PFH-NPs aggregated in SKOV3 cells (in vitro) and the nude xenograft tumour region when combined with folic acid receptors. When triggered by low-intensity focused ultrasound (LIFU), FURH-PFH-NPs released PFH, UCNPs-RB and HCPT. The above procedure was monitored through multimodal imaging, which simultaneously guided the tumour therapy. UCNPs-RB and PFH promoted the PDT effect under LIFU. Through PDT and HCPT, we obtained better therapeutic effects and good biosafety against SKOV3 nude xenograft tumours. FURH-PFH-NPs combined with LIFU and laser irradiation might be a promising strategy for ovarian cancer.


Subject(s)
Fluorescent Dyes/administration & dosage , Fluorocarbons/administration & dosage , Nanoparticles/administration & dosage , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Photochemotherapy , Rose Bengal/administration & dosage , Theranostic Nanomedicine , Animals , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Female , Humans , Lasers , Light , Mice, Nude , Multimodal Imaging , Neoplasms/pathology
5.
Mol Pharm ; 17(3): 817-826, 2020 03 02.
Article in English | MEDLINE | ID: mdl-31910019

ABSTRACT

Biomedical nanoplatforms have been widely investigated for ultrasound (US) imaging and cancer therapy. Herein, perfluorocarbon (PFC) is encapsulated into biocompatible polydopamine (PDA) to form a theranostic nanosystem, followed by the modification of polyethylene glycol (PEG) to stabilize the nanoparticle via a facile one-pot method. Under 808 nm near-infrared laser irradiation, PDA can generate hyperthermia to transform PFC droplets to bubbles with high US imaging sensitivity. The US imaging detection of the PFC-PDA-PEG nanosystem is achievable in a time span of up to 25 min in vitro at a low US frequency and mechanical index, manifesting a US imaging performance for in vivo application. Moreover, tumor cells incubated with the nanosystem are ablated effectively under laser irradiation at 808 nm. The results illustrate the potential of the PDA-based theranostic agent in US imaging-guided photothermal therapy of tumor.


Subject(s)
Drug Delivery Systems/methods , Fluorocarbons/administration & dosage , Hyperthermia, Induced/methods , Indoles/administration & dosage , Infrared Rays/therapeutic use , Nanoparticles/chemistry , Photothermal Therapy/methods , Polymers/administration & dosage , Animals , Capsules , Cell Survival/drug effects , Contrast Media , Female , Fluorocarbons/chemistry , HCT116 Cells , Human Umbilical Vein Endothelial Cells , Humans , Indoles/chemistry , Mice , Mice, Inbred BALB C , Mice, Nude , Polyethylene Glycols/chemistry , Polymers/chemistry , Tumor Burden/drug effects , Ultrasonography/methods , Xenograft Model Antitumor Assays
6.
Biomater Sci ; 7(10): 4060-4074, 2019 Oct 01.
Article in English | MEDLINE | ID: mdl-31475710

ABSTRACT

Combined photothermal-chemotherapy guided by multimodal imaging is a promising strategy for cancer diagnosis and treatment. Multifunctional nanoparticles, such as those comprising organic and inorganic compounds, have been extensively investigated for combined photothermal-chemotherapy; however, their application is still limited by their potential long-term toxicity and lack of contrast properties. To solve these problems, in this study, a new type of multifunctional nanoparticle for combined photothermal-chemotherapy guided by dual-modality imaging was prepared with endogenous melanin by multistep emulsification to enhance tumor ablation. The nanoparticles were coated with poly(lactide-co-glycolic acid) (PLGA) and loaded with paclitaxel (PTX), encapsulated melanin and perfluoropentane (PFP). The materials in the nanoparticles were endogenous, ensuring high stability, biocompatibility, and biosafety. Nanoparticles irradiated with a laser, which induced their phase transformation into microbubbles, exhibited high photothermal conversion efficiency, thereby achieving photoacoustic (PA)/ultrasound (US) dual-modality imaging to determine tumor location, boundary, and size and to monitor drug distribution. Furthermore, optical droplet vaporization (ODV) of the nanoparticles could trigger the release of PTX; thus, these nanoparticles are a useful drug carrier. In vivo and in vitro experiments revealed that a strong synergistic antitumor effect was achieved by combining the photothermal properties of the nanoparticles with a chemotherapy drug. Importantly, the cavitation, thermoelastic expansion, and sonoporation caused by the phase transformation of the nanoparticles could directly damage the tumors. These processes also promoted the release, penetration and absorption of the drug, further enhancing the effect of combined photothermal-chemotherapy on tumor suppression. Therefore, the multifunctional nanoparticles prepared in this study provide a new strategy of using endogenous materials for controlled near-infrared (NIR)-responsive drug release and combined photothermal-chemotherapy guided by multimodal imaging.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Fluorocarbons/administration & dosage , Melanins/administration & dosage , Nanoparticles/administration & dosage , Neoplasms/therapy , Paclitaxel/administration & dosage , Polylactic Acid-Polyglycolic Acid Copolymer/administration & dosage , Animals , Antineoplastic Agents, Phytogenic/pharmacokinetics , Cell Line, Tumor , Cell Survival/drug effects , Combined Modality Therapy , Delayed-Action Preparations/administration & dosage , Female , Fluorocarbons/pharmacokinetics , Human Umbilical Vein Endothelial Cells , Humans , Melanins/pharmacokinetics , Mice, Inbred BALB C , Neoplasms/metabolism , Paclitaxel/pharmacokinetics , Photoacoustic Techniques , Phototherapy , Polylactic Acid-Polyglycolic Acid Copolymer/pharmacokinetics , Tissue Distribution , Ultrasonography
7.
Drug Deliv ; 26(1): 147-157, 2019 Dec.
Article in English | MEDLINE | ID: mdl-30822171

ABSTRACT

Hypoxic pulmonary vasoconstriction (HPV) is a well-characterized vascular response to low oxygen pressures and is involved in life-threatening conditions such as high-altitude pulmonary edema (HAPE) and pulmonary arterial hypertension (PAH). While the efficacy of oral therapies can be affected by drug metabolism, or dose-limiting systemic toxicity, inhaled treatment via pressured metered dose inhalers (pMDI) may be an effective, nontoxic, practical alternative. We hypothesized that a stable water-in-perfluorooctyl bromide (PFOB) emulsion that provides solubility in common pMDI propellants, engineered for intrapulmonary delivery of pulmonary vasodilators, reverses HPV during acute hypoxia (HX). Male Sprague Dawley rats received two 10-min bouts of HX (13% O2) with 20 min of room air and drug application between exposures. Treatment groups: intrapulmonary delivery (PUL) of (1) saline; (2) ambrisentan in saline (0.1 mg/kg); (3) empty emulsion; (4) emulsion encapsulating ambrisentan or sodium nitrite (NaNO2) (0.1 and 0.5 mg/kg each); and intravenous (5) ambrisentan (0.1 mg/kg) or (6) NaNO2 (0.5 mg/kg). Neither PUL of saline or empty emulsion, nor infusions of drugs prevented pulmonary artery pressure (PAP) elevation (32.6 ± 3.2, 31.5 ± 1.2, 29.3 ± 1.8, and 30.2 ± 2.5 mmHg, respectively). In contrast, PUL of aqueous ambrisentan and both drug emulsions reduced PAP by 20-30% during HX, compared to controls. IL6 expression in bronchoalveolar lavage fluid and whole lung 24 h post-PUL did not differ among cohorts. We demonstrate proof-of-concept for delivering pulmonary vasodilators via aerosolized water-in-PFOB emulsion. This concept opens a potentially feasible and effective route of treating pulmonary vascular pathologies via pMDI.


Subject(s)
Drug Delivery Systems/methods , Emulsions/administration & dosage , Fluorocarbons/administration & dosage , Hypertension, Pulmonary/drug therapy , Pulmonary Edema/drug therapy , Water/administration & dosage , Animals , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/metabolism , Drug Evaluation, Preclinical/methods , Emulsions/metabolism , Fluorocarbons/metabolism , Hypertension, Pulmonary/diagnostic imaging , Hypertension, Pulmonary/metabolism , Male , Phenylpropionates/administration & dosage , Phenylpropionates/metabolism , Pulmonary Circulation/drug effects , Pulmonary Circulation/physiology , Pulmonary Edema/diagnostic imaging , Pulmonary Edema/metabolism , Pyridazines/administration & dosage , Pyridazines/metabolism , Rats , Rats, Sprague-Dawley , Treatment Outcome , Water/metabolism
9.
Int J Pharm ; 552(1-2): 312-318, 2018 Dec 01.
Article in English | MEDLINE | ID: mdl-30308268

ABSTRACT

In the field of dermal drug delivery, determining the penetration depth of actives is a standard procedure for the development of novel formulations. Regarding the vehicle components, respective penetration studies are rather scarce due to their often challenging analytics. However, an understanding of the interactions between drugs and additives during skin penetrating could help to develop promising drug delivery systems. Thus, the objective of the present study was to simultaneously monitor the skin penetration of the incorporated model drug diclofenac sodium and the semifluorinated oil perfluorohexyloctane (F6H8) from newly developed nanoemulsions. In vitro tape stripping studies were conducted and the tapes were analysed for their content of drug and additive in parallel by HPLC and 19F NMR. The penetration depth and total recovered amount of both substances of interest were successfully determined on each tape strip. The vehicle oil compound F6H8 itself showed a very small skin penetration, while the penetration of diclofenac sodium was consistently about 9- to 10-fold higher. Higher amounts of the oil content led to higher skin penetration of diclofenac sodium and slightly increased oil penetration; this effect might be explained by the increasing occlusion effect caused by increasing amounts of fluorinated oil.


Subject(s)
Diclofenac/administration & dosage , Fluorocarbons/administration & dosage , Lecithins/administration & dosage , Nanoparticles/administration & dosage , Oils/administration & dosage , Skin Absorption , Animals , Emulsions , Skin/metabolism , Swine
10.
J Indian Soc Pedod Prev Dent ; 36(3): 296-300, 2018.
Article in English | MEDLINE | ID: mdl-30246753

ABSTRACT

BACKGROUND: Injection of local anesthesia is one of the most important reasons for avoidance behavior in children. Applying a topical anesthetic before injection is the most popular way to control pain; however, topical anesthetics have some shortcomings such as longer duration of action, displeasing taste, and spread of the anesthetic agent to noninjection site areas. Cryoanesthesia using refrigerant as a topical anesthesia is being studied as an alternative to overcome the shortcomings of topical anesthetics and has shown promising results. MATERIALS AND METHODS: In this split-mouth design study, 50 children of aged 8-10 years who required bilateral mandibular local anesthesia administration were selected. In the first visit, application of topical anesthetic spray (lidocaine) on one side and during the second appointment cryoanesthetic tetrafluorethane on the other side was used before local anesthetic administration. Patients were asked to report their discomfort and pain using visual analog scale (VAS) (subjective method). Patients' pain perception during injection is assessed by sound, eye, and motor (SEM) scale by the dentist (objective method). RESULTS: The results were statistically analyzed using paired Wilcoxon signed-rank test and Mann-Whitney tests. In VAS scale (subjective method), pain scores were significantly lower in tetrafluorethane group when compared with lidocaine group. In SEM scale (objective method), pain scores were lower in tetrafluorethane group when compared with lidocaine group, but it was statistically insignificant. CONCLUSION: Precooling the injection site using refrigerant tetrafluorethane spray has shown to be effective in eliminating pain before local anesthesia administration in children when compared with topical anesthetic lidocaine spray.


Subject(s)
Anesthesia, Dental/methods , Anesthesia, Local/methods , Cryoanesthesia/methods , Fluorocarbons/administration & dosage , Pain Perception/drug effects , Aerosols , Anesthetics, Local/administration & dosage , Child , Facial Pain/prevention & control , Humans , Injections/adverse effects , Lidocaine/administration & dosage , Pain Measurement , Pain, Postoperative/prevention & control , Pulpectomy/adverse effects , Tooth Extraction/adverse effects
11.
Nat Rev Neurol ; 14(6): 325-337, 2018 06.
Article in English | MEDLINE | ID: mdl-29674752

ABSTRACT

After ischaemic stroke, brain damage can be curtailed by rescuing the 'ischaemic penumbra' - that is, the severely hypoperfused, at-risk but not yet infarcted tissue. Current evidence-based treatments involve restoration of blood flow so as to salvage the penumbra before it evolves into irreversibly damaged tissue, termed the 'core'. Intravenous thrombolysis (IVT) can salvage the penumbra if given within 4.5 h after stroke onset; however, the early recanalization rate is only ~30%. Direct removal of the occluding clot by mechanical thrombectomy considerably improves outcomes over IVT alone, but despite early recanalization in > 80% of cases, ~50% of patients who receive this treatment do not enjoy functional independence, usually because the core is already too large at the time of recanalization. Novel therapies aiming to 'freeze' the penumbra - that is, prevent core growth until recanalization is complete - hold potential as adjuncts to mechanical thrombectomy. This Review focuses on nonpharmacological approaches that aim to restore the physiological balance between oxygen delivery to and oxygen demand of the penumbra. Particular emphasis is placed on normobaric oxygen therapy, hypothermia and sensory stimulation. Preclinical evidence and early pilot clinical trials are critically reviewed, and future directions, including clinical translation and trial design issues, are discussed.


Subject(s)
Balloon Occlusion/methods , Brain Ischemia/therapy , Electric Stimulation Therapy/methods , Evoked Potentials , Fluorocarbons/pharmacology , Hypothermia, Induced/methods , Ischemic Preconditioning/methods , Mechanical Thrombolysis/methods , Oxygen Inhalation Therapy/methods , Stroke/therapy , Thrombolytic Therapy/methods , Animals , Combined Modality Therapy , Fluorocarbons/administration & dosage , Humans
12.
Biomaterials ; 165: 1-13, 2018 05.
Article in English | MEDLINE | ID: mdl-29500978

ABSTRACT

As a highly biocompatible NIR dye, indocyanine green (ICG) has been widely explored for cancer treatment due to its various energy level transition pathways upon NIR light excitation simultaneously, which leads to different theranostic effects (eg. Photoacoustic (PA) and fluorescence imaging (FL), photodynamic and photothermal therapy (PDT&PTT)). However, the theranostic efficiency of ICG is restricted intrinsically, owing to the competitive relationship of its co-existing imaging and therapeutic effect. Moreover, the extrinsic hypoxia nature of tumor further limits its therapeutic effect, especially for the oxygen-dependent PDT. Herein, perfluorooctyl bromide (PFOB), another biocompatible chemical, was integrated with ICG in a nanoliposome structure via a facile two-step emulsion method. Such an ICG&PFOB co-loaded nanoliposomes (LIP-PFOB-ICG) realized computed tomography (CT) contrast imaging in vivo, providing better anatomical information of tumor in comparison to ICG enabled PA and FL imaging. More importantly, LIP-PFOB-ICG inhibited MDA-MB-231 tumor growth completely via intravenous injection through enhanced PDT&PTT synergistic therapy due to the excellent oxygen carrying ability of PFOB, which effectively attenuated tumor hypoxia, improved the efficiency of collisional energy transfer between ICG and oxygen and reduced the expression of heat shock protein (HSP). As expected, the introduction of PFOB within nanoliposomes with ICG has augmented the theranostic effect of ICG comprehensively, which makes this simple biocompatible liposome-based nanoagent a potential candidate for clinical imaging guided phototherapy of cancer.


Subject(s)
Fluorocarbons , Indocyanine Green , Liposomes , Multimodal Imaging , Nanoparticles , Photochemotherapy , Animals , Cell Line, Tumor , Contrast Media/administration & dosage , Contrast Media/chemistry , Fluorocarbons/administration & dosage , Fluorocarbons/chemistry , Humans , Hydrocarbons, Brominated , Indocyanine Green/administration & dosage , Indocyanine Green/chemistry , Liposomes/chemistry , Mice, Inbred BALB C , Multimodal Imaging/methods , Nanoparticles/chemistry , Oxygen/metabolism , Photochemotherapy/methods , Tumor Hypoxia
13.
J Control Release ; 264: 219-227, 2017 Oct 28.
Article in English | MEDLINE | ID: mdl-28867377

ABSTRACT

We study the influence of ultrasound on paclitaxel-loaded nanocapsules in vitro and in vivo. These nanocapsules possess a shell of poly(dl-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) and a liquid core of perfluorooctyl bromide (PFOB). In vitro experiments show that mechanical effects such as cavitation are negligible for nanocapsules due to their small size and thick and rigid shell. As the mechanical effects were unable to increase paclitaxel delivery, we focused on the thermal effects of ultrasound in the in vivo studies. A focused ultrasound sequence was therefore optimized in vivo under magnetic resonance imaging guidance to obtain localized mild hyperthermia with high acoustic pressure. Ultrasound-induced mild hyperthermia (41-43°C) was then tested in vivo in a subcutaneous CT-26 colon cancer murine model. As hyperthermia is applied, an inhibition of tumor growth for both paclitaxel-loaded nanocapsules and the commercial formulation of paclitaxel, namely Taxol® have been observed (p<0.05). Ultrasound-induced mild hyperthermia at high acoustic pressure appears as an interesting strategy to enhance cytotoxic efficacy locally.


Subject(s)
Antineoplastic Agents, Phytogenic/administration & dosage , Hyperthermia, Induced , Nanocapsules/administration & dosage , Paclitaxel/administration & dosage , Ultrasonic Therapy , Animals , Antineoplastic Agents, Phytogenic/pharmacokinetics , Antineoplastic Agents, Phytogenic/therapeutic use , Cell Line, Tumor , Combined Modality Therapy , Female , Fluorocarbons/administration & dosage , Fluorocarbons/pharmacokinetics , Fluorocarbons/therapeutic use , Hydrocarbons, Brominated , Mice, Nude , Nanocapsules/therapeutic use , Neoplasms/metabolism , Neoplasms/therapy , Paclitaxel/pharmacokinetics , Paclitaxel/therapeutic use , Polyethylene Glycols/administration & dosage , Polyethylene Glycols/pharmacokinetics , Polyethylene Glycols/therapeutic use , Polyglactin 910/administration & dosage , Polyglactin 910/pharmacokinetics , Polyglactin 910/therapeutic use , Tissue Distribution , Treatment Outcome
15.
Theranostics ; 7(4): 846-854, 2017.
Article in English | MEDLINE | ID: mdl-28382158

ABSTRACT

Activating droplets vaporization has become an attractive strategy for ultrasound imaging and physical therapy due to the significant increase in ultrasound backscatter signals and its ability to physically damage the tumor cells. However, the current two types of transitional droplets named after their activation methods have their respective limitations. To circumvent the limitations of these activation methods, here we report the concept of magnetic droplet vaporization (MDV) for stimuli-responsive cancer theranostics by a magnetic-responsive phase-transitional agent. This magnetic-sensitive phase-transitional agent-perfluorohexane (PFH)-loaded porous magnetic microspheres (PFH-PMMs), with high magnetic-thermal energy-transfer capability, could quickly respond to external alternating current (AC) magnetic fields to produce thermal energy and trigger the vaporization of the liquid PFH. We systematically demonstrated MDV both in vitro and in vivo. This novel trigger method with deep penetration can penetrate the air-filled viscera and trigger the vaporization of the phase-transitional agent without the need of pre-focusing lesion. This unique MDV strategy is expected to substantially broaden the biomedical applications of nanotechnology and promote the clinical treatment of tumors that are not responsive to chemical therapies.


Subject(s)
Contrast Media/administration & dosage , Ferrosoferric Oxide/administration & dosage , Fluorocarbons/administration & dosage , Magnetics , Microspheres , Volatilization , Animals , Disease Models, Animal , Hyperthermia, Induced/methods , Mice, Nude , Neoplasms/diagnostic imaging , Neoplasms/therapy , Phase Transition/radiation effects , Ultrasonography/methods
16.
Theranostics ; 7(3): 562-572, 2017.
Article in English | MEDLINE | ID: mdl-28255351

ABSTRACT

Perfluorocarbon nanoemulsions (PFCNEs) have recently been undergoing rigorous study to investigate their ability to improve the therapeutic efficacy of tumor ablation by high intensity focused ultrasound (HIFU). For precise control of PFCNE delivery and thermal ablation, their accumulation and distribution in a tumor should be quantitatively analyzed. Here, we used fluorine-19 (19F) magnetic resonance imaging (MRI) to quantitatively track PFCNE accumulation in a tumor, and analyzed how intra-tumoral PFCNE quantities affect the therapeutic efficacy of HIFU treatment. Ablation outcomes were assessed by intra-voxel incoherent motion analysis and bioluminescent imaging up to 14 days after the procedure. Assessment of PFCNE delivery and treatment outcomes showed that 2-3 mg/mL of PFCNE in a tumor produces the largest ablation volume under the same HIFU insonation conditions. Histology showed varying degrees of necrosis depending on the amount of PFCNE delivered. 19F MRI promises to be a valuable platform for precisely guiding PFCNE-enhanced HIFU ablation of tumors.


Subject(s)
Ablation Techniques/methods , Carcinoma/diagnostic imaging , Carcinoma/therapy , Fluorine-19 Magnetic Resonance Imaging/methods , Fluorocarbons/administration & dosage , Hyperthermia, Induced/methods , Sonication/methods , Animals , Carcinoma/pathology , Disease Models, Animal , Emulsions/administration & dosage , Histocytochemistry , Mice, Inbred BALB C , Mice, Nude , Transplantation, Heterologous , Treatment Outcome
17.
Food Chem Toxicol ; 100: 24-33, 2017 Feb.
Article in English | MEDLINE | ID: mdl-27939831

ABSTRACT

Perfluorononanoic acid (PFNA) is a perfluoroalkyl substance (PFAS) that is structurally related to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Whereas PFOA and PFOS are known immunotoxicants, PFNA is less well characterized. Our previous study showed that PFNA has immunomodulatory effects on leukocyte populations and immune function. The present studies sought to determine whether, and to what degree, the immune system recovered 28 days after PFNA exposure. None of the parameters measured had fully recovered. A few parameters had partially recovered, including decreased spleen size and the decreased ratio of the CD4+/CD8+ double-positive population in thymus. The majority of effects of PFNA remained unchanged 28 days after exposure, including decreased proportion of intact thymocytes (as determined by FSC vs SSC), alterations in the ratios of immune cell populations in spleen and the CD4+, CD8+ and double-negative populations in thymus. Notably, PFNA markedly increased the TNFα response to LPS in vivo, and no recovery was evident 28 days after exposure. The effect of PFNA on CD4+ T cells, CD8+ T cells and CD19+ cells was more pronounced in females. The current study demonstrates that a single high dose exposure to PFNA (e.g. as might occur accidentally in an occupational setting) has long-lasting effects on the immune system.


Subject(s)
Fluorocarbons/pharmacology , Immune System/drug effects , Immune System/immunology , Organ Size/drug effects , Animals , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Fatty Acids , Female , Flow Cytometry , Fluorocarbons/administration & dosage , Male , Mice , Mice, Inbred C57BL , Spleen/drug effects , Thymocytes/drug effects
18.
J Nanosci Nanotechnol ; 16(3): 2201-9, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27455619

ABSTRACT

This paper successfully fabricated a novel multifunctional theranostic agent (PFOB@PLA/GO/Gd-DTPA NCs) by loading perfluorooctylbromide (PFOB) into poly(lactic acid) (PLA) nanocapsules (NCs) followed by surface functionalization with graphene oxide (GO) and gadolinium-chelate (Gd-DTPA). It was found that the resulting nanoagent could serve as a contrast agent simultaneously to enhance ultrasound (US) and magnetic resonance imaging (MRI). Benefiting from the strong absorption in the near infrared (NIR) region, the nanocapsules could efficiently kill cancer cells under NIR laser irradiation. Thus, such a single theranostic agent with the combination of realtime US imaging and high-resolution MR imaging could achieve great therapeutic effectiveness without systemic damage to the body. In addition, the cytotoxicity assay on HUVEC cells revealed a good biocompatibility of PFOB@PLA/GO/Gd-DTPA NCs, showing that the versatile nanocapsule system may hold great potential as an effective nanoplatform for contrast enhanced imaging guided photothermal therapy.


Subject(s)
Chelating Agents/chemistry , Fluorocarbons/administration & dosage , Gadolinium/chemistry , Graphite/chemistry , Lactic Acid/chemistry , Nanocapsules , Neoplasms/therapy , Polymers/chemistry , Biocompatible Materials , Fluorocarbons/chemistry , HeLa Cells , Human Umbilical Vein Endothelial Cells , Humans , Hydrocarbons, Brominated , Hyperthermia, Induced , Magnetic Resonance Imaging/methods , Neoplasms/diagnostic imaging , Neoplasms/pathology , Oxides/chemistry , Phototherapy , Polyesters , Ultrasonography/methods
19.
Eur J Ophthalmol ; 26(5): 491-6, 2016 Aug 04.
Article in English | MEDLINE | ID: mdl-26742873

ABSTRACT

PURPOSE: To investigate the short-term safety and efficacy of autologous platelet-rich plasma (a-PRP) as adjuvant to pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling in the treatment of highly myopic macular holes (MH). METHODS: This was a prospective, nonrandomized interventional case series. Patients with MH associated with high myopia, with or without previous PPV, were included. All patients underwent 23-G PPV with the use of a-PRP. Anatomical and functional results of surgery were recorded. RESULTS: We included 7 eyes of 6 patients with highly myopic MH. Primary anatomical success was achieved in 7 out of 7 eyes. Mean best-corrected visual acuity improved by more than 1 line from baseline (0.66 ± 0.36 LogMAR) to final visit (0.52 ± 0.25 logMAR), but with no statistically significant difference (p = 0.246, Wilcoxon test). No surgical-related complications were noticed. CONCLUSIONS: The use of a-PRP as adjuvant to PPV with ILM peeling is effective in the treatment of highly myopic MH. This approach may represent a valid alternative to the inverted ILM flap technique, with comparable visual and anatomical results and the advantage of a simpler procedure. Further studies are necessary to confirm its usefulness in the management of high myopic MH.


Subject(s)
Myopia, Degenerative/therapy , Platelet-Rich Plasma , Retinal Perforations/therapy , Vitrectomy , Aged , Basement Membrane/surgery , Endotamponade , Female , Fluorocarbons/administration & dosage , Humans , Intravitreal Injections , Male , Middle Aged , Myopia, Degenerative/complications , Myopia, Degenerative/diagnostic imaging , Prospective Studies , Retinal Perforations/diagnostic imaging , Retinal Perforations/etiology , Retrospective Studies , Silicone Oils/administration & dosage , Tomography, Optical Coherence , Treatment Outcome , Visual Acuity
20.
Graefes Arch Clin Exp Ophthalmol ; 254(6): 1069-73, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26340867

ABSTRACT

PURPOSE: To determine whether ophthalmic viscoelastic devices (OVDs) can be used during vitrectomy to prevent perflorocarbon liquid (PFCL) from leaking into the subretinal space through retinal tears in eyes with proliferative vitreoretinopathy (PVR). The OVDs are adhesive materials that can temporally close retinal breaks. We introduce a "soft shell technique", which allows the unfolding of the retina by PFCL. METHODS: We studied five eyes of five patients with proliferative vitreoretinopathy that underwent vitrectomy using the soft shell technique. After removing the core vitreous, the OVDs were carefully injected over the area where confluent retinal folds were formed with possible retinal breaks. This created a soft shell shield on the retina that can prevent the intravitreal PFCL from leaking into the subretinal space. RESULTS: The soft shell technique still allowed the PFCL to unfold the retina even if iatrogenic breaks are present. The high viscosity of OVDs sealed the iatrogenic retinal breaks and thus prevented the PFCL from leaking into the subretinal space during the vitrectomy. All patients had an improvement of the visual acuity, and four eyes had a reattachment of the retina. CONCLUSIONS: Although only five eyes were examined, the success of the soft shell technique indicates that it can be used with PFCL, which facilitates the unfolding of the contracted retina.


Subject(s)
Fluorocarbons/administration & dosage , Retinal Detachment/surgery , Viscosupplements/administration & dosage , Vitrectomy/methods , Vitreoretinopathy, Proliferative/surgery , Adult , Aged , Chondroitin Sulfates/administration & dosage , Drainage/methods , Drug Combinations , Humans , Hyaluronic Acid/administration & dosage , Laser Coagulation , Male , Middle Aged , Silicone Oils
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