scholarly journals Gold Nanoplates as Cancer-Targeted Photothermal Actuators for Drug Delivery and Triggered Release

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Tyler Brann ◽  
Dhruvinkumar Patel ◽  
Rajat Chauhan ◽  
Kurtis T. James ◽  
Paula J. Bates ◽  
...  
Keyword(s):  
Near Infrared ◽  
Blue Shift ◽  
Selective Exposure ◽  
Chemotherapeutic Agents ◽  
Hydrodynamic Diameter ◽  
Laser Exposure ◽  
Triggered Release ◽  
Plasmon Resonance Peak ◽  
Fluorescence Measurements

The selective exposure of cancerous tissue to systemically delivered chemotherapeutic agents remains a major challenge facing cancer therapy. To address this question, a near infrared responsive oligonucleotide-coated (AS1411, hairpin, or both) gold nanoplate loaded with doxorubicin is demonstrated to be nontoxic to cells without triggered release, while being acutely toxic to cells after 5 minutes of laser exposure to trigger DOX release. Conjugation of oligonucleotides to the nanoplates is confirmed by an average increase in hydrodynamic diameter of 30.6 nm, an average blue shift of the plasmon resonance peak by 36 nm, and an average −10 mV shift in zeta potential of the particles. DOX loading through intercalation into the hairpin DNA structure is confirmed through fluorescence measurements. For both GNP-Hairpin and GNP-Hairpin-AS1411, ~60% of loaded DOX is released after the first 5 minutes of laser exposure (λ=817 nm), with complete release after two more 5-minute exposures. Preliminary proof of concept is demonstrated in vitro using A549 and MDA-MB-231 cell lines as models for breast and lung cancer, respectively. Exposure of cells to untriggered DOX-loaded conjugate with no laser exposure results in little to no toxicity, while laser-triggered release of DOX causes significant cell death.

scholarly journals Three-Step Synthesis of a Redox-Responsive Blend of PEG–block–PLA and PLA and Application to the Nanoencapsulation of Retinol

Polymers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2350
Author(s):  
Louise Van Gheluwe ◽  
Eric Buchy ◽  
Igor Chourpa ◽  
Emilie Munnier
Keyword(s):  
Disulfide Bond ◽  
High Efficiency ◽  
Aqueous Suspension ◽  
Human Keratinocytes ◽  
Hydrodynamic Diameter ◽  
Triggered Release ◽  
Active Molecule ◽  
Polymeric Nanocarriers ◽  
Redox Responsive

Smart polymeric nanocarriers have been developed to deliver therapeutic agents directly to the intended site of action, with superior efficacy. Herein, a mixture of poly(lactide) (PLA) and redox-responsive poly(ethylene glycol)–block–poly(lactide) (PEG–block–PLA) containing a disulfide bond was synthesized in three steps. The nanoprecipitation method was used to prepare an aqueous suspension of polymeric nanocarriers with a hydrodynamic diameter close to 100 nm. Retinol, an anti-aging agent very common in cosmetics, was loaded into these smart nanocarriers as a model to measure their capacity to encapsulate and to protect a lipophilic active molecule. Retinol was encapsulated with a high efficiency with final loading close to 10% w/w. The stimuli-responsive behavior of these nanocarriers was demonstrated in vitro, in the presence of l-Glutathione, susceptible to break of disulfide bond. The toxicity was low on human keratinocytes in vitro and was mainly related to the active molecule. Those results show that it is not necessary to use 100% of smart copolymer in a nanosystem to obtain a triggered release of their content.

Optophoresis Accurately Predicts Response to Chemotherapy in CLL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4834-4834
Author(s):  
Patricia McNeeley ◽  
Alan Saven ◽  
Ilona Kariv ◽  
Jorge Nieva ◽  
Philippe Marchand ◽  
...  
Keyword(s):  
Near Infrared ◽  
Ex Vivo ◽  
Chemotherapeutic Agents ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Functional Responses ◽  
Chemotherapy Administration ◽  
Response To Chemotherapy ◽  
Fluorescent Tags

Abstract In vitro drug resistance assays have shown efficacy in predicting response to chemotherapeutic drugs in a number of solid tumors. In chronic lymphocytic leukemia (CLL) many assays are limited by the difficulty involved in culturing these cells ex vivo. We have developed a novel, optical-based methodology that is sensitive to broad cellular physical characteristics, such as morphology, size, refractive index, density and surface properties. This measurement, known as Optophoresis, quantifies cell motion induced by exposure to a moving optical gradient, generated from a near-infrared laser beam (Forster AH, et al. Anal Biochem 2004, 327(1):14–22 and Wang MM, et al. Appl Opt 2003, 42(28):5765–73). In Optophoresis small numbers of cells are analyzed intact, in their native state. No labels are required for quantification of functional responses, but cell subpopulations may be identified using fluorescent tags. We have used this assay to predict response to chemotherapeutic agents in patients with CLL. Methods: We performed Optophoresis with six drugs (fludarabine, chlorambucil, vincristine, cyclophosphamide, cladribine and prednisolone) on 74 CLL patient samples. 68 of these were classic B-CLL; there was one hairy cell variant, two were T-CLL, two evolved to PLL and one evolved to lymphoma. 21 of the samples were from patients for whom clinical data on response to chemotherapy was available for 33 drug treatments. Response to therapy was defined as a decrease in RAI stage. Results: 21 patients aged 58 to 93 years; 71% Rai stage III or IV were included in this analysis. Six patients were evaluated prospectively, with the assay performed before chemotherapy administration, and 15 patients were evaluated retrospectively with the assay performed after a course of treatment. Optophoresis accurately predicted response to chemotherapy in 88% of the 33 treatments evaluated. In the four instances for which the Optophoresis results did not match the retrospective clinical outcome; the patient was historically sensitive to treatment and Optophoresis results indicated current resistance to the drug. Subsequent resistance to drug therapy is known to occur in a significant percentage of treated CLL patients. Conclusion: Optophoresis of CLL cells accurately predicts response to chemotherapy in CLL. Further studies using results of Optophoresis to guide CLL treatment are warranted.

scholarly journals Macrophage as cellular vehicles for delivery of nanoparticles

2014 ◽  
Vol 07 (03) ◽  
pp. 1450023 ◽  
Author(s):  
Song Feng ◽  
Sisi Cui ◽  
Jing Jin ◽  
Yueqing Gu
Keyword(s):  
Central Nervous System ◽  
Near Infrared ◽  
Folate Receptor ◽  
Drug Carriers ◽  
Chemotherapeutic Agents ◽  
Tumor Bearing ◽  
The Central Nervous System ◽  
Clearing Rate ◽  
Nir Dye

Treatment of malignant brain tumors continues to challenge scientists and clinicians alike. Location of these tumors within the central nervous system (CNS), which is considered a "privileged" organ, can prevent the penetration of chemotherapeutic agents through the blood–brain barrier (BBB). To overcome this limitation, nanoparticles are taken up and transported by macrophage and then delivered directly into the CNS. In this study, we used macrophage to uptake the folate-targeted bifunctional micelles loaded with near-infrared (NIR) dye ICG-Der-01 and investigate the dynamic bio-distributions of macrophage after intravenous injection into tumor-bearing mice. In vitro cellular experiments by confocal microscopy indicated that the uptake of micelles in macrophage was greatly enhanced due to the folate receptor overexpression. Dynamic bio-distributions of macrophage showed a rapid clearing rate through the liver intestine pathway. In conclusion, macrophage could potentially be used as nanoparticle drug carriers and require further investigation.

scholarly journals Ultrasound-triggered Release of Calcein and Doxorubicin from HER2-targeted Liposomes in Breast Cancer Therapy

2020 ◽  
Author(s):  
Amal El Amir ◽  
Saniha Ajith ◽  
Nour AlSawaftah ◽  
Waad Abuwatfa ◽  
Debasmita Mukhopadhyay ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Monoclonal Antibody ◽  
Growth Factor Receptor ◽  
Low Frequency ◽  
Chemotherapeutic Agents ◽  
Breast Cancer Cell Lines ◽  
Triggered Release ◽  
Her2 Positive ◽  
Potential Strategy

Abstract The functionalization of liposomes with antibodies is a potential strategy to increase the specificity of liposomes and reduce side-effects of chemotherapeutic agents. The active targeting of Human Epidermal growth factor Receptor 2 (HER2) positive breast cancer cells can be achieved by coating liposomes with an anti-HER2 monoclonal antibody. In this study, we synthesized Calcein and Doxorubicin loaded immunoliposomes functionalized with the monoclonal antibody Trastuzumab. Both liposomes were characterized for size, phospholipid concentration and antibody conjugation. The effect of low-frequency ultrasound (LFUS)-induced drug release was tested using three power densities, 7.46, 9.85 and 17.31 mW/cm2; and the release data were modeled using six different kinetic models. LFUS results established the sonosensitivity of both carrier types, with immunoliposomes being more acoustically sensitive than control liposomes. Results also showed an increase in the release rate as the power density increased from 7.46 to 17.31 mW/cm2. Finally, the in vitro cell experiments showed enhanced uptake and cytotoxicity when breast cancer cell lines, SKBr3 and MDAMB-231, were treated with LFUS-triggered HER-liposomes.

scholarly journals Comparative Study of the Optical and Heat Generation Properties of IR820 and Indocyanine Green

2012 ◽  
Vol 11 (2) ◽  
pp. 7290.2011.00031 ◽  
Author(s):  
Alicia Fernandez-Fernandez ◽  
Romila Manchanda ◽  
Tingjun Lei ◽  
Denny A. Carvajal ◽  
Yuan Tang ◽  
...  
Keyword(s):  
Indocyanine Green ◽  
Near Infrared ◽  
Experimental Models ◽  
Cyanine Dye ◽  
Laser Exposure ◽  
Fluorescence Signal ◽  
Thermal Generation ◽  
Significant Difference

Near-infrared (NIR) fluorophores are the focus of extensive research for combined molecular imaging and hyperthermia. In this study, we showed that the cyanine dye IR820 has optical and thermal generation properties similar to those of indocyanine green (ICG) but with improved in vitro and in vivo stability. The fluorescent emission of IR820 has a lower quantum yield than ICG but less dependence of the emission peak location on concentration. IR820 demonstrated degradation half-times approximately double those of ICG under all temperature and light conditions in aqueous solution. In hyperthermia applications, IR820 generated lower peak temperatures than ICG (4–9%) after 3-minute laser exposure. However, there was no significant difference in hyperthermia cytotoxicity, with both dyes causing significant cell growth inhibition at concentrations ≥ 5 μM. Fluorescent images of cells with 10 μM IR820 were similar to ICG images. In rats, IR820 resulted in a significantly more intense fluorescence signal and significantly higher organ dye content than for ICG 24 hours after intravenous dye administration ( p < .05). Our study shows that IR820 is a feasible agent in experimental models of imaging and hyperthermia and could be an alternative to ICG when greater stability, longer image collection times, or more predictable peak locations are desirable.

scholarly journals Near-Infrared Light-Responsive Shell-Crosslinked Micelles of Poly(d,l-lactide)-b-poly((furfuryl methacrylate)-co-(N-acryloylmorpholine)) Prepared by Diels–Alder Reaction for the Triggered Release of Doxorubicin

Materials ◽  
2021 ◽  
Vol 14 (24) ◽  
pp. 7913
Author(s):  
Sonyabapu Yadav ◽  
Kalyan Ramesh ◽  
Parveen Kumar ◽  
Sung-Han Jo ◽  
Seong II Yoo ◽  
...  
Keyword(s):  
Drug Release ◽  
Near Infrared ◽  
Click Reaction ◽  
In Vitro Cytotoxicity ◽  
Diels Alder ◽  
Infrared Light ◽  
Burst Release ◽  
Crosslinking Reaction ◽  
Triggered Release

In the present study, we developed near-infrared (NIR)-responsive shell-crosslinked (SCL) micelles using the Diels–Alder (DA) click reaction between an amphiphilic copolymer poly(d,l-lactide)20-b-poly((furfuryl methacrylate)10-co-(N-acryloylmorpholine)78) (PLA20-b-P(FMA10-co-NAM78)) and a diselenide-containing crosslinker, bis(maleimidoethyl) 3,3′-diselanediyldipropionoate (BMEDSeDP). The PLA20-b-P(FMA10-co-NAM78) copolymer was synthesized by RAFT polymerization of FMA and NAM using a PLA20-macro-chain transfer agent (PLA20-CTA). The DA reaction between BMEDSeDP and the furfuryl moieties in the copolymeric micelles in water resulted in the formation of SCL micelles. The SCL micelles were analyzed by 1H-NMR, FE-SEM, and DLS. An anticancer drug, doxorubicin (DOX), and an NIR sensitizer, indocyanine green (ICG), were effectively incorporated into the SCL micelles during the crosslinking reaction. The DOX/ICG-loaded SCL micelles showed pH- and NIR-responsive drug release, where burst release was observed under NIR laser irradiation. The in vitro cytotoxicity analysis demonstrated that the SCL was not cytotoxic against normal HFF-1 cells, while DOX/ICG-loaded SCL micelles exhibited significant antitumor activity toward HeLa cells. Thus, the SCL micelles of PLA20-b-P(FMA10-co-NAM78) can be used as a potential delivery vehicle for the controlled drug release in cancer therapy.

scholarly journals Dynamic phototuning of 3D hydrogel stiffness

2015 ◽  
Vol 112 (7) ◽  
pp. 1953-1958 ◽  
Author(s):  
Ryan S. Stowers ◽  
Shane C. Allen ◽  
Laura J. Suggs
Keyword(s):  
Near Infrared ◽  
Infrared Light ◽  
External Control ◽  
Cell Phenotype ◽  
Biological Processes ◽  
Triggered Release ◽  
In Vivo Experiments ◽  
Cellular Microenvironments

Hydrogels are widely used as in vitro culture models to mimic 3D cellular microenvironments. The stiffness of the extracellular matrix is known to influence cell phenotype, inspiring work toward unraveling the role of stiffness on cell behavior using hydrogels. However, in many biological processes such as embryonic development, wound healing, and tumorigenesis, the microenvironment is highly dynamic, leading to changes in matrix stiffness over a broad range of timescales. To recapitulate dynamic microenvironments, a hydrogel with temporally tunable stiffness is needed. Here, we present a system in which alginate gel stiffness can be temporally modulated by light-triggered release of calcium or a chelator from liposomes. Others have shown softening via photodegradation or stiffening via secondary cross-linking; however, our system is capable of both dynamic stiffening and softening. Dynamic modulation of stiffness can be induced at least 14 d after gelation and can be spatially controlled to produce gradients and patterns. We use this system to investigate the regulation of fibroblast morphology by stiffness in both nondegradable gels and gels with degradable elements. Interestingly, stiffening inhibits fibroblast spreading through either mesenchymal or amoeboid migration modes. We demonstrate this technology can be translated in vivo by using deeply penetrating near-infrared light for transdermal stiffness modulation, enabling external control of gel stiffness. Temporal modulation of hydrogel stiffness is a powerful tool that will enable investigation of the role that dynamic microenvironments play in biological processes both in vitro and in well-controlled in vivo experiments.

Effect of pH, ultrasound frequency and power density on the release of calcein from stealth liposomes

2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Salma E. Ahmed ◽  
Hesham G. Moussa ◽  
Ana M. Martins ◽  
Mohammad H. Al-Sayah ◽  
Ghaleb A. Husseini
Keyword(s):  
Power Density ◽  
In Vitro Study ◽  
Chemotherapeutic Agents ◽  
Triggered Release ◽  
Pegylated Liposomes ◽  
Stealth Liposomes ◽  
Ultrasound Frequency ◽  
Model Drug ◽  
Power Densities

AbstractThe use of liposomes as carriers for chemotherapeutic agents in combination with ultrasound as a stimulus to control the time and space of the drug release is a promising approach for cancer treatment, as it can reduce the side effects caused by conventional chemotherapy. This in vitro study investigated the triggered release of calcein from stealth (PEGylated) and non-stealth (non-PEGylated) liposomes, using ultrasound at low (20 kHz) and high (1 and 3 MHz) frequencies, and at different power densities. Release was monitored by the increase in fluorescence due to relieving of calcein’s self-quenching upon dilution when the model drug leaks out of the liposomes. The results showed that, independent of the power density, the release was highest at 20 kHz. For the same frequency, release usually increased with increasing power densities. Additionally, for release at 20 kHz, a comparison was done for PEGylated and non-PEGylated liposomes, at two pH values: 5.2 and 7.4. The results were then compared to previously published studies. In all cases, the mechanism of release seems to involve cavitation events that either pierce a hole in or shear open the liposomes, as all the determined power densities are above the transient cavitation threshold.

scholarly journals Near-Infrared MAO A Inhibitor (NMI) Outperformed FDA-Approved Chemotherapeutic Agents in Brain and Other Cancers: A Bioinformatic Analysis of NCI60 Screening Data

2021 ◽  
Vol 11 (10) ◽  
pp. 1318
Author(s):  
Qianhua Feng ◽  
Yuxuan Lian ◽  
Yihan Qian ◽  
Jean C. Shih
Keyword(s):  
Prostate Cancer ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Near Infrared ◽  
Chemotherapeutic Agents ◽  
Monoamine Oxidase A ◽  
Mao A ◽  
Cns Cancer ◽  
Cancer Prostate

Our previous work has shown that monoamine oxidase A (MAO A) is overexpressed in glioma and prostate cancer. Near-infrared dye conjugate MAO A Inhibitor (NMI) inhibited the growth of these cancers. This study investigated the effects of NMI on other cancers by NCI60 screening. Our results showed that 48 out of 59 screened cell lines from nine types of cancer had 100% growth inhibition at 10 μM NMI treatment. The in vitro efficacy of NMI determined by growth inhibition (GI50 and TGI) and lethal doses (LC50) has been further studied in various cell lines of CNS cancer, prostate cancer, and non-small cell lung cancer (NSCLC), these three cancers showed increased MAO A expression in tumors compared to normal tissues. Based on the waterfall plots and the 3D scatter plot of GI50, TGI, and LC50 data, NMI showed higher potency to several CNS cancer and NSCLC cell lines than prostate cancer cell lines. In vitro efficacy of NMI outperformed FDA-approved drugs for CNS cancer, prostate cancer, and NSCLC, respectively. The Pairwise Pearson Correlation Coefficient (PCC) showed that NMI has a unique mechanism compared to the existing anticancer drugs. This study shows that NMI is a novel theragnostic drug with high potency and unique mechanisms for brain, prostate, NSCLC, and other cancers.

scholarly journals pH-Sensitive and Long-Circulation Nanoparticles for Near-Infrared Fluorescence Imaging-Monitored and Chemo-Photothermal Synergistic Treatment Against Gastric Cancer

2020 ◽  
Vol 11 ◽  
Author(s):  
Yun Zhou ◽  
Xuanzi Sun ◽  
Liansuo Zhou ◽  
Xiaozhi Zhang
Keyword(s):  
Gastric Cancer ◽  
Near Infrared ◽  
Therapeutic Option ◽  
Drug Loading ◽  
Gastric Cancer Cell Line ◽  
Postoperative Treatment ◽  
Maximum Temperature ◽  
Hydrodynamic Diameter

Gastrectomy is the primary therapeutic option for gastric cancer. Postoperative treatment also plays a crucial role. The strategy to improve the postoperative prognosis of gastric cancer requires a combined system that includes a more efficient synergistic treatment and real-time monitoring after surgery. In this study, photothermal-chemotherapy combined nanoparticles (PCC NPs) were prepared via π-π stacking to perform chemo-photothermal synergistic therapy and continuous imaging of gastric cancer. PCC NPs had a spherical morphology and good monodispersity under aqueous conditions. The hydrodynamic diameter of PCC NPs was 59.4 ± 3.6 nm. PCC NPs possessed strong encapsulation ability, and the maximum drug loading rate was approximately 37%. The NPs exhibited extraordinary stability and pH-response release profiles. The NPs were rapidly heated under irradiation. The maximum temperature was close to 58°C. PCC NPs showed good biocompatibility both in vitro and in vivo. Moreover, the NPs could effectively be used for in vivo continuous monitoring of gastric cancer. After one injection, the fluorescent signal remained in tumor tissues for nearly a week. The inhibitory effect of PCC NPs was evaluated in a gastric cancer cell line and xenograft mouse model. Both in vitro and in vivo evaluations demonstrated that PCC NPs could be used for chemo-photothermal synergistic therapy. The suppression effect of PCC NPs was significantly better than that of single chemotherapy or photothermal treatment. This study lays the foundation for the development of novel postoperative treatments for gastric cancer.

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