scholarly journals Tumor Environment-Responsive Hyaluronan Conjugated Zinc Protoporphyrin for Targeted Anticancer Photodynamic Therapy

2021 ◽  
Vol 11 (2) ◽  
pp. 136
Author(s):  
Shanghui Gao ◽  
Rayhanul Islam ◽  
Jun Fang
Keyword(s):  
Photodynamic Therapy ◽  
Water Solubility ◽  
Polymeric Micelles ◽  
Tumor Model ◽  
Micelle Formation ◽  
Light Irradiation ◽  
Zinc Protoporphyrin ◽  
Tumor Environment

Targeted tumor accumulation, tumor environment responsive drug release, and effective internalization are critical issues being considered in developing anticancer nanomedicine. In this context, we synthesized a tumor environment-responsive nanoprobe for anticancer photodynamic therapy (PDT) that is a hyaluronan conjugated zinc protoporphyrin via an ester bond (HA-es-ZnPP), and we examined its anticancer PDT effect both in vitro and in vivo. HA-es-ZnPP exhibits high water-solubility and forms micelles of ~40 nm in aqueous solutions. HA-es-ZnPP shows fluorescence quenching without apparent 1O2 generation under light irradiation because of micelle formation. However, 1O2 was extensively generated when the micelle is disrupted, and ZnPP is released. Compared to native ZnPP, HA-es-ZnPP showed lower but comparable intracellular uptake and cytotoxicity in cultured mouse C26 colon cancer cells; more importantly, light irradiation resulted in 10-time increased cytotoxicity, which is the PDT effect. In a mouse sarcoma S180 solid tumor model, HA-es-ZnPP as polymeric micelles exhibited a prolonged systemic circulation time and the consequent tumor-selective accumulation based on the enhanced permeability and retention (EPR) effect was evidenced. Consequently, a remarkable anticancer PDT effect was achieved using HA-es-ZnPP and a xenon light source, without apparent side effects. These findings suggest the potential of HA-es-ZnPP as a candidate anticancer nanomedicine for PDT.

scholarly journals The Topical Nanodelivery of Vismodegib Enhances Its Skin Penetration and Performance In Vitro While Reducing Its Toxicity In Vivo

Pharmaceutics ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 186
Author(s):  
Maria Natalia Calienni ◽  
Daniela Maza Vega ◽  
C. Facundo Temprana ◽  
María Cecilia Izquierdo ◽  
David E. Ybarra ◽  
...  
Keyword(s):  
Side Effects ◽  
Water Solubility ◽  
Polymeric Micelles ◽  
Skin Penetration ◽  
Distribution Volume ◽  
And Performance ◽  
Oral Doses ◽  
Advanced Basal Cell Carcinoma

Vismodegib is a first-in-class inhibitor for advanced basal cell carcinoma treatment. Its daily oral doses present a high distribution volume and several side effects. We evaluated its skin penetration loaded in diverse nanosystems as potential strategies to reduce side effects and drug quantities. Ultradeformable liposomes, ethosomes, colloidal liquid crystals, and dendrimers were able to transport Vismodegib to deep skin layers, while polymeric micelles failed at this. As lipidic systems were the most effective, we assessed the in vitro and in vivo toxicity of Vismodegib-loaded ultradeformable liposomes, apoptosis, and cellular uptake. Vismodegib emerges as a versatile drug that can be loaded in several delivery systems for topical application. These findings may be also useful for the consideration of topical delivery of other drugs with a low water solubility.

The effects of photodynamic therapy with Photodithazine on HPV 16 E6/E7 associated cervical cancer model

2011 ◽  
Vol 15 (03) ◽  
pp. 174-180 ◽  
Author(s):  
Lan Ying Wen ◽  
Su-Mi Bae ◽  
Jin Hwan Do ◽  
Kye-Shin Park ◽  
Woong Shick Ahn
Keyword(s):  
Cervical Cancer ◽  
Photodynamic Therapy ◽  
Growth Inhibition ◽  
Biological Significance ◽  
Light Irradiation ◽  
Tumor Growth Inhibition ◽  
Cancer Model ◽  
Hpv 16

Photodynamic therapy (PDT) is a promising treatment for cancer that has been recently accepted in the clinic. In this study, we examined a biological significance of PDT with a chlorin-based photosensitizer, Photodithazine, on cervical cancer model. When human papillomavirus type 16 (HPV16)- transformed mouse TC-1 cells were exposed to varied doses of Photodithazine with light irradiation (6.25 J/cm2), the significant growth inhibition of TC-1 cells was observed at 0.75 μg/mL of Photodithazine. The damaged cells by Photodithazine/PDT were categorized to be early and late apoptosis, as determined by annexin V staining. Photodithazine was primarily localized at lysosome apparatus within TC-1 cells while it was rapidly accumulated and sustained for initial 3 h in tumor tissue of TC-1 tumor bearing mice after IV injection. The tumor growth inhibition by Photodithazine/PDT with light irradiation (300 J/cm2) was examined after injection of various concentration of Photodithazine in tumor mice system. Our results show that Photodithazine/PDT might have significant advantages in the selective killing of tumor lesions in HPV 16 E6/E7 associated cervical cancer model, both in vitro and in vivo.

scholarly journals Use of Cyclodextrins in Anticancer Photodynamic Therapy Treatment

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1936 ◽  
Author(s):  
Amina Ben Mihoub ◽  
Ludivine Larue ◽  
Albert Moussaron ◽  
Zahraa Youssef ◽  
Ludovic Colombeau ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Photodynamic Therapy ◽  
Molecular Oxygen ◽  
Inclusion Complexes ◽  
Water Solubility ◽  
Cellular Damage ◽  
Hybrid Nanoparticles ◽  
Binding Modes

Photodynamic therapy (PDT) is mainly used to destroy cancerous cells; it combines the action of three components: a photoactivatable molecule or photosensitizer (PS), the light of an appropriate wavelength, and naturally occurring molecular oxygen. After light excitation of the PS, the excited PS then reacts with molecular oxygen to produce reactive oxygen species (ROS), leading to cellular damage. One of the drawbacks of PSs is their lack of solubility in water and body tissue fluids, thereby causing low bioavailability, drug-delivery efficiency, therapeutic efficacy, and ROS production. To improve the water-solubility and/or drug delivery of PSs, using cyclodextrins (CDs) is an interesting strategy. This review describes the in vitro or/and in vivo use of natural and derived CDs to improve antitumoral PDT efficiency in aqueous media. To achieve these goals, three types of binding modes of PSs with CDs are developed: non-covalent CD–PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies. This review is divided into three parts: (1) non-covalent CD-PS inclusion complexes, covalent CD–PS conjugates, and CD–PS nanoassemblies, (2) incorporating CD–PS systems into hybrid nanoparticles (NPs) using up-converting or other types of NPs, and (3) CDs with fullerenes as PSs.

scholarly journals Development and Evaluation of 2-Amino-7-Fluorophenazine 5,10-Dioxide Polymeric Micelles as Antitumoral Agents for 4T1 Breast Cancer

Polymers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 71
Author(s):  
Nicole Lecot ◽  
Belén Dávila ◽  
Carina Sánchez ◽  
Marcelo Fernández ◽  
Mercedes González ◽  
...  
Keyword(s):  
Polymeric Micelles ◽  
Metastatic Breast ◽  
Stage Iv ◽  
Tumor Model ◽  
Infrared Analysis ◽  
Biological Studies ◽  
Potential Applications ◽  
4T1 Breast Cancer

2-Amino-7-fluorophenazine 5,10-dioxide (FNZ) is a bioreducible prodrug, poorly soluble in water, with potential anticancer activity on hypoxic-tumors. This poor solubility limits its potential applications in clinic. Amphiphilic pristine polymeric micelles (PMs) based on triblock copolymers Pluronic® and Tetronic®, glycosylated derivatives and their mixtures with preformed-liposomes (LPS), were analyzed as strategies to improve the bioavailability of FNZ. FNZ encapsulations were performed and the obtaining nanostructures were characterized using UV-visible spectroscopy (UV-VIS), Transmission Electron Microscopy (TEM), Fourier transform infrared analysis and Dynamic Light Scattering (DLS). The most promising nanoformulations were analyzed for their potential toxicity and pharmacologically, at 20 mg/kg FNZ-doses, in a stage-IV murine metastatic-breast tumor model. The results revealed that the solubility of the encapsulated-FNZ increased up to seven times and the analysis (UV-VIS, DLS and TEM) confirmed the interaction between vehicles and FNZ. In all the cases appropriate encapsulation efficiencies (up to 70%), monodisperse nanometric particle sizes (PDI = 0.180–0.335), adequate Z-potentials (−1.59 to −26.4 mV), stabilities and spherical morphologies were obtained. The in vitro profile of FNZ controlled releases corresponded mainly to a kinetic Higuchi model. The in vitro/in vivo biological studies revealed non-toxicity and relevant tumor-weight diminution (up to 61%).

Quercetin Loaded Nanoparticles in Targeting Cancer: Recent Development

2019 ◽  
Vol 19 (13) ◽  
pp. 1560-1576 ◽  
Author(s):  
Manjula Vinayak ◽  
Akhilendra K. Maurya
Keyword(s):  
Silver Nanoparticles ◽  
Clinical Application ◽  
Glycolic Acid ◽  
Water Solubility ◽  
Polymeric Micelles ◽  
Metastatic Cancer ◽  
Chitosan Nanoparticles ◽  
Drug Carriers

:The spread of metastatic cancer cell is the main cause of death worldwide. Cellular and molecular basis of the action of phytochemicals in the modulation of metastatic cancer highlights the importance of fruits and vegetables. Quercetin is a natural bioflavonoid present in fruits, vegetables, seeds, berries, and tea. The cancer-preventive activity of quercetin is well documented due to its anti-inflammatory, anti-proliferative and anti-angiogenic activities. However, poor water solubility and delivery, chemical instability, short half-life, and low-bioavailability of quercetin limit its clinical application in cancer chemoprevention. A better understanding of the molecular mechanism of controlled and regulated drug delivery is essential for the development of novel and effective therapies. To overcome the limitations of accessibility by quercetin, it can be delivered as nanoconjugated quercetin. Nanoconjugated quercetin has attracted much attention due to its controlled drug release, long retention in tumor, enhanced anticancer potential, and promising clinical application. The pharmacological effect of quercetin conjugated nanoparticles typically depends on drug carriers used such as liposomes, silver nanoparticles, silica nanoparticles, PLGA (Poly lactic-co-glycolic acid), PLA (poly(D,L-lactic acid)) nanoparticles, polymeric micelles, chitosan nanoparticles, etc.:In this review, we described various delivery systems of nanoconjugated quercetin like liposomes, silver nanoparticles, PLGA (Poly lactic-co-glycolic acid), and polymeric micelles including DOX conjugated micelles, metal conjugated micelles, nucleic acid conjugated micelles, and antibody-conjugated micelles on in vitro and in vivo tumor models; as well as validated their potential as promising onco-therapeutic agents in light of recent updates.

Lactose-conjugated porphyrin: Synthesis and photobiological evaluation as potential agents for photodynamic therapy

2021 ◽  
Author(s):  
Yue Cao ◽  
Xin Zhang ◽  
Bo Ren ◽  
Xiaodong Yang
Keyword(s):  
Photodynamic Therapy ◽  
Water Solubility ◽  
Application Range ◽  
Porphyrin Derivatives ◽  
The Poor ◽  
Specific Cytotoxicity ◽  
Tumor Selectivity ◽  
Porphyrin Synthesis

Porphyrin-based photosensitizers are conventional photodynamic agents applied in clinic. However, their clinic application has been overshadowed by the poor water solubility. In addition, they have weak tumor selectivity, which may cause undesirable side effects. The preparation of novel porphyrin derivatives has been explored for the potential application in photodynamic therapy (PDT). To achieve this goal, lactose-conjugated porphyrin nanoparticles (Lac-PorNPs) has been synthesized and characterized. PDT with Lac-PorNPs exhibits tumor-specific cytotoxicity in lactose receptor overexpressed HepG2 cells in vitro and in vivo. In summary, we designed and synthesized lactose conjugates porphyrin with enhanced water-solubility and tumor selectivity. This work expanded the application range of porphyrin-based photosensitizers for cancer treatment.

scholarly journals The Use of Ultrasound and Micelles in Cancer Treatment

2008 ◽  
Vol 8 (5) ◽  
pp. 2205-2215 ◽  
Author(s):  
Ghaleb A. Husseini ◽  
William G. Pitt
Keyword(s):  
Drug Delivery ◽  
Polymeric Micelles ◽  
Tumor Model ◽  
Therapeutic Window ◽  
Rat Tumor Model ◽  
Drug Potency ◽  
Potential Benefits

The high toxicity of potent chemotherapeutic drugs like Doxorubicin (Dox) limits the therapeutic window in which they can be applied. This window can be expanded by controlling the drug delivery in both space and time such that non-targeted tissues are not adversely affected. Recent research has shown that ultrasound (US) can be used to control the release of Dox and other hydrophobic drugs from polymeric micelles in both time and space. It has also been shown using an in vivo rat tumor model that Dox activity can be enhanced by ultrasound in one region, while in an adjacent region there is little or no effect of the drug. In this article, we review the in vivo and in vitro research being conducted in the area of using ultrasound to enhance and target micellar drug delivery to cancerous tissues. Additionally, we summarize our previously published mathematical models that attempt to represent the release and re-encapsulation phenomena of Dox from Pluronic® P105 micelles upon the application of ultrasound. The potential benefits of such controlled chemotherapy compels a thorough investigation of the role of ultrasound (US) and the mechanisms by which US accomplishes drug release and/or enhances drug potency. Therefore we will summarize our findings related to the mechanism involved in acoustically activated micellar drug delivery to tumors.

scholarly journals Self-Guiding Polymeric Prodrug Micelles with Two Aggregation-Induced Emission Photosensitizers for Enhanced Chemo-Photodynamic Therapy

2021 ◽  
Author(s):  
Xiaoqing Yi ◽  
Jingjing Hu ◽  
Jun Dai ◽  
Xiaoding Lou ◽  
Zujin Zhao ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cellular Uptake ◽  
Continuous Light ◽  
Light Irradiation ◽  
Fluorescence Signal ◽  
Aggregation State ◽  
Aggregation Induced Emission ◽  
Dual Stage

<p>Nowadays, aggregation-induced emission luminogens (AIEgens) with reactive oxygen species (ROS) generating ability have been used as photosensitizers for imaging guided photodynamic therapy (PDT). To achieve enhanced antitumor outcomes, combining AIEgens-based PDT with chemotherapy is an efficient strategy. However, the therapeutic efficiency is hampered by the limited cellular uptake efficiency and the appropriate light irradiation occasion. In this paper, a self-guiding polymeric micelle (TB@PMPT) composed of two AIE photosensitizers and a reduction-sensitive paclitaxel prodrug (PTX-SS-N<sub>3</sub>) was established for enhanced chemo-photodynamic therapy by a dual-stage light irradiation strategy. When the micelles were accumulated in tumor tissues, the first light irradiation (L<sub>1</sub>, 6 min) was utilized to facilitate cellular uptake by “photochemical internalization” (PCI). Then the intracellular glutathione (GSH) would induce the PTX release, micelles disassembly and the aggregation state change of AIEgens. The fluorescence signal change of two AIEgens-based ratiometric fluorescent probe could not only precisely guide the second light irradiation (L<sub>2</sub>, 18 min) for sufficient ROS production, but also monitor the non-fluorescent drug PTX release in turn. Both <i>in vivo</i> and <i>in vitro</i> studies demonstrated that the dual-stage light irradiation strategy employed for TB@PMPT micelles exhibited superior therapeutic effect than only 24-min continuous light irradiation.<br></p>

scholarly journals Multifunctional AIE iridium (III) photosensitizer nanoparticles for two-photon-activated imaging and mitochondria targeting photodynamic therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xuzi Cai ◽  
Kang-Nan Wang ◽  
Wen Ma ◽  
Yuanyuan Yang ◽  
Gui Chen ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Water Solubility ◽  
Tissue Imaging ◽  
Ros Generation ◽  
Generation Efficiency ◽  
Deep Tissue ◽  
Two Photon ◽  
Mitochondria Targeting

AbstractDeveloping novel photosensitizers for deep tissue imaging and efficient photodynamic therapy (PDT) remains a challenge because of the poor water solubility, low reactive oxygen species (ROS) generation efficiency, serve dark cytotoxicity, and weak absorption in the NIR region of conventional photosensitizers. Herein, cyclometalated iridium (III) complexes (Ir) with aggregation-induced emission (AIE) feature, high photoinduced ROS generation efficiency, two-photon excitation, and mitochondria-targeting capability were designed and further encapsulated into biocompatible nanoparticles (NPs). The Ir-NPs can be used to disturb redox homeostasis in vitro, result in mitochondrial dysfunction and cell apoptosis. Importantly, in vivo experiments demonstrated that the Ir-NPs presented obviously tumor-targeting ability, excellent antitumor effect, and low systematic dark-toxicity. Moreover, the Ir-NPs could serve as a two-photon imaging agent for deep tissue bioimaging with a penetration depth of up to 300 μm. This work presents a promising strategy for designing a clinical application of multifunctional Ir-NPs toward bioimaging and PDT.

scholarly journals Self-Guiding Polymeric Prodrug Micelles with Two Aggregation-Induced Emission Photosensitizers for Enhanced Chemo-Photodynamic Therapy

2021 ◽  
Author(s):  
Xiaoqing Yi ◽  
Jingjing Hu ◽  
Jun Dai ◽  
Xiaoding Lou ◽  
Zujin Zhao ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cellular Uptake ◽  
Continuous Light ◽  
Light Irradiation ◽  
Fluorescence Signal ◽  
Aggregation State ◽  
Aggregation Induced Emission ◽  
Dual Stage

<p>Nowadays, aggregation-induced emission luminogens (AIEgens) with reactive oxygen species (ROS) generating ability have been used as photosensitizers for imaging guided photodynamic therapy (PDT). To achieve enhanced antitumor outcomes, combining AIEgens-based PDT with chemotherapy is an efficient strategy. However, the therapeutic efficiency is hampered by the limited cellular uptake efficiency and the appropriate light irradiation occasion. In this paper, a self-guiding polymeric micelle (TB@PMPT) composed of two AIE photosensitizers and a reduction-sensitive paclitaxel prodrug (PTX-SS-N<sub>3</sub>) was established for enhanced chemo-photodynamic therapy by a dual-stage light irradiation strategy. When the micelles were accumulated in tumor tissues, the first light irradiation (L<sub>1</sub>, 6 min) was utilized to facilitate cellular uptake by “photochemical internalization” (PCI). Then the intracellular glutathione (GSH) would induce the PTX release, micelles disassembly and the aggregation state change of AIEgens. The fluorescence signal change of two AIEgens-based ratiometric fluorescent probe could not only precisely guide the second light irradiation (L<sub>2</sub>, 18 min) for sufficient ROS production, but also monitor the non-fluorescent drug PTX release in turn. Both <i>in vivo</i> and <i>in vitro</i> studies demonstrated that the dual-stage light irradiation strategy employed for TB@PMPT micelles exhibited superior therapeutic effect than only 24-min continuous light irradiation.<br></p>

Sign in / Sign up

Export Citation Format

Share Document