Carboxymethyl-hexanoyl Chitosan Nanodroplets for Ultrasonic Imaging and Drug Delivery to Tumor

2018 ◽  
Vol 24 (15) ◽  
pp. 1682-1688 ◽  
Author(s):  
Yu Jinsui ◽  
Situ Bing ◽  
Luo Muhua ◽  
Li Yue ◽  
Liao Jianyi ◽  
...  
Keyword(s):  
Ultrasound Imaging ◽  
Tumor Therapy ◽  
Carboxymethyl Chitosan ◽  
Great Promise ◽  
Ovarian Cancer Cells ◽  
Mechanical Index ◽  
Surface Charges ◽  
Particle Structure ◽  
Drug Release Profile ◽  
Hexanoyl Chitosan

Introduction: Although a great many strategies have been proposed for tumor-targeted chemotherapy, current delivery methods of anticancer drugs present limited success with inevitable systemic toxicity. The aim of this study was to develop a new kind of theranostic carrier for targeted tumor therapy. Methods: Prior to prepare CHC-PFP-DOX, carboxymethyl-hexanoyl chitosan (CHC) was synthesized by acylation of carboxymethyl chitosan. To develop CHC-PFP, perfluoropentane (PFP), an ultrasound gas precursor, was simultaneously encapsulated into the hydrophobic inner cores of pre-formulated CHC micelle in aqueous phase via using the oil in water (O/W) emulsion method. The size distribution and surface charges of these nanodroplets were measured and the morphology was observed by transmission electron microscopy (TEM). For ultrasound imaging application, in vitro model was established to evaluate the imaging of CHC-PFP-DOX under different concentration and mechanical index. After that, the anti-tumor effect of ultrasound combined with CHC-PFPDOX on ovarian cancer cells was investigated. Results: The resulting CHC-PFP-DOX had a nano-sized particle structure, with hydrophobic anticancer DOX/PFP inner cores and a hydrophilic carboxymethyl chitosan polymer outer shell. The favorable nano-scaled size offers the potential to extravagate from veins and accumulate in tumor tissues via enhanced permeation and retention (EPR) effect. Additionally, CHC-PFP-DOX showed the ability to serve as ultrasound imaging agent at body temperature. Notably, it exhibited an ultrasound-triggered drug release profile through the external ultrasound irradiation. Further study demonstrated that ultrasound combined with CHC-PFP-DOX can improve the killing effect of chemotherapy for tumor. Conclusion: CHC-PFP-DOX holds great promise in simultaneous cancer-targeting ultrasound imaging and ultrasound- mediated delivery for cancer chemotherapy.

Bifunctional scaffolds of hydroxyapatite/poly(dopamine)/carboxymethyl chitosan with osteogenesis and anti-osteosarcoma effect

2021 ◽  
Author(s):  
Mengyu Yao ◽  
Qingxia Zou ◽  
Wenwu Zou ◽  
Zhenze Xie ◽  
Zhihao Li ◽  
...  
Keyword(s):  
Bone Tumor ◽  
Tumor Therapy ◽  
Carboxymethyl Chitosan

Bifunctional scaffolds prepared by hydroxyapatite/poly(dopamine)/carboxymethyl chitosan with good osteogenesis and anti-osteosarcoma effect is promising for bone tumor therapy.

Charge-conversion and ultrasound-responsive O-carboxymethyl chitosan nanodroplets for controlled drug delivery

Nanomedicine ◽  
2019 ◽  
Vol 14 (19) ◽  
pp. 2549-2565 ◽  
Author(s):  
Dong Meng ◽  
Lu Guo ◽  
Dandan Shi ◽  
Xiao Sun ◽  
Mengmeng Shang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Tumor Cells ◽  
Drug Delivery System ◽  
Ultrasound Imaging ◽  
Delivery System ◽  
Cell Interaction ◽  
Carboxymethyl Chitosan ◽  
Ultrasound Exposure ◽  
Interaction Efficiency

Aim: O-carboxymethyl chitosan/perfluorohexane nanodroplets (O-CS NDs) and doxorubicin-loading O-carboxymethyl chitosan nanodroplets were synthesized and functionally tested as drug delivery system in vitro. Materials & methods: The characteristics, charge conversion, stability, cytotoxicity, ultrasound imaging ability, interaction with tumor cells of the nanodroplets and eradication on tumor cells of the doxorubicin-loaded nanodroplets were investigated. Results: O-CS NDs (below 200 nm) achieved higher tumor cellular associations at acidic pH, with great serum stability, pH-dependent charge conversion and good ultrasound imaging ability. Doxorubicin-loading O-carboxymethyl chitosan nanodroplets exhibited strong cytotoxicity on PC-3 cells with ultrasound exposure. Conclusion: These stable, safe and smart O-CS NDs may be a promising approach to improve cell interaction efficiency as an ultrasound imaging and cancer-targeting drug delivery system.

A Novel Chitosan Microbubble as Ultrasound-Triggered Drug Carrier for Antitumor In Vitro

2014 ◽  
Vol 636 ◽  
pp. 139-143
Author(s):  
Song Shen ◽  
Bei Ding ◽  
Qing Li ◽  
Xu Wei Yu ◽  
Xue Yong Qi ◽  
...  
Keyword(s):  
Drug Release ◽  
Drug Carrier ◽  
Tumor Therapy ◽  
Carboxymethyl Chitosan ◽  
Ultrasound Contrast Agents ◽  
Ultrasound Contrast ◽  
Triggered Drug Release ◽  
Ultrasound Assisted ◽  
Potential Strategy

Uniform Microbubbles (MBs) were routinely used as ultrasound contrast agents, but the MBs served for drug carrier showed well-marked advantage. In this study, we prepared a novel docetaxel–loaded microbubbles by carboxymethyl chitosan with W/O/W emulsion technique. Then, the surface morphology was characterized by scanning electron microscope (SEM). Ultrasound-triggered drug release experiments were performed with adjustable intensity and time. In the antitumor experiment in vitro, Ultrasound-assisted drug release from MBs exhibited good treatment of tumor. The results proved the combination of ultrasound and drug-loaded carboxymethyl chitosan microbubbles could be used as a potential strategy for anti-tumor therapy.

scholarly journals Preparation of Clindamycin Hydrochloride Loaded De-Esterified Low-Methoxyl Mango Peel Pectin Film Used as a Topical Drug Delivery System

Polymers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1006 ◽  
Author(s):  
Tanpong Chaiwarit ◽  
Pornchai Rachtanapun ◽  
Nutthapong Kantrong ◽  
Pensak Jantrawut
Keyword(s):  
Drug Loading ◽  
Antibacterial Activities ◽  
Great Promise ◽  
Drug Release Profile ◽  
Film Forming ◽  
Cutibacterium Acnes ◽  
Alternative Material ◽  
Mango Peel ◽  
The Fourier Transform ◽  
Puncture Strength

In this study, we aimed to develop a low-mexthoxyl pectin (LMP) from mango peel pectin through a de-esterification method for use as a film forming agent. The prepared de-esterified pectin (DP) was compared to commercial LMP (cLMP) which possessed a 29% degree of esterification (DE). Mango peel pectin was extracted from ripe Nam Dokmai mango peel using the microwave-assisted extraction method. Pectin derived from the mango peel was classified as a high mexthoxyl pectin (79% DE) with 75% of galacturonic acid (GalA) content. A de-esterification experiment was designed by central composite design to plot the surface response curve. Our prepared DP was classified as LMP (DE 29.40%) with 69% GalA. In addition, the Fourier-transform infrared spectrophotometer (FTIR) spectra of the DP were similar to cLMP and the pectin backbone was not changed by the de-esterification process. Strikingly, the cLMP and DP films showed non-significant differences between their physical properties (p > 0.05) with respect to the puncture strength (13.72 N/mm2 and 11.13 N/mm2 for the cLMP and DP films, respectively), percent elongation (2.75% and 2.52% for the cLMP and DP films, respectively), and Young’s modulus (67.69 N/mm2 and 61.79 N/mm2 for the cLMP and DP films, respectively). The de-esterified pectin containing clindamycin HCl (DPC) and low-methoxyl pectin containing clindamycin HCl (cLMPC) films demonstrated 93.47% and 98.79% of drug loading content. The mechanical properties of the cLMPC and DPC films were improved possibly due to their crystal structures and a plasticizing effect of clindamycin HCl loaded into the films. The DPC film exhibited a drug release profile similar to that of the cLMPC film. Our anti-bacterial test of the films found that the cLMPC film showed 41.11 and 76.30 mm inhibitory clear zones against Staphylococcus aureus and Cutibacterium acnes, respectively. The DPC film showed 40.78 and 74.04 mm clear zones against S. aureus and C. acnes, respectively. The antibacterial activities of the cLMPC and DPC films were not significantly different from a commercial clindamycin solution. The results of this study suggest that mango peel pectin can be de-esterified and utilized as an LMP and the de-esterified pectin has the potential for use as a film forming agent, similar to cLMP. In addition, the remarkable use of de-esterified mango peel pectin to prepare films, as shown by our study, holds a great promise as an alternative material for anti-bacterial purposes.

scholarly journals Engineering of Doxorubicin-Encapsulating and TRAIL-Conjugated Poly(RGD) Proteinoid Nanocapsules for Drug Delivery Applications

Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 2996
Author(s):  
Elad Hadad ◽  
Safra Rudnick-Glick ◽  
Ella Itzhaki ◽  
Matan Y. Avivi ◽  
Igor Grinberg ◽  
...  
Keyword(s):  
Side Effects ◽  
Self Assembly ◽  
Tumor Therapy ◽  
Ovarian Cancer Cells ◽  
Chemotherapeutic Drug ◽  
Enzyme Degradation ◽  
Wide Range ◽  
Step Growth ◽  
Step Growth Polymerization ◽  
Necrosis Factor

Proteinoids are non-toxic biodegradable polymers prepared by thermal step-growth polymerization of amino acids. Here, P(RGD) proteinoids and proteinoid nanocapsules (NCs) based on D-arginine, glycine, and L-aspartic acid were synthesized and characterized for targeted tumor therapy. Doxorubicin (Dox), a chemotherapeutic drug used for treatment of a wide range of cancers, known for its adverse side effects, was encapsulated during self-assembly to form Dox/P(RGD) NCs. In addition, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which can initiate apoptosis in most tumor cells but undergoes fast enzyme degradation, was stabilized by covalent conjugation to hollow P(RGD) NCs. The effect of polyethylene glycol (PEG) conjugation was also studied. Cytotoxicity tests on CAOV-3 ovarian cancer cells demonstrated that Dox/P(RGD) and TRAIL-P(RGD) NCs were as effective as free Dox and TRAIL with cell viability of 2% and 10%, respectively, while PEGylated NCs were less effective. Drug-bearing P(RGD) NCs offer controlled release with reduced side effects for improved therapy.

scholarly journals Novel CD44-Targeting and pH/redox Dual-Stimuli Responsive Core-Shell Nanoparticles Loading Triptolide to Combat Breast Cancer Growth and Lung Metastasis

2021 ◽  
Author(s):  
Jinfeng Shi ◽  
Yali Ren ◽  
Jiaqi Ma ◽  
Xi Luo ◽  
Jiaxin Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Release ◽  
Lung Metastasis ◽  
Cancer Progression ◽  
Drug Loading ◽  
Tumor Therapy ◽  
Systemic Toxicity ◽  
Migration And Invasion ◽  
Drug Release Profile ◽  
Cd44 Targeting

Abstract BackgroundThe toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited its clinical application. Therefore, we fabricated a CD44-targeting and tumor-microenvironment pH/redox sensitive nanosystem, composed by hyaluronic acid-Vitamin E succinate (HA-VE) and Poly (β-Amino Esters) (PBAEss) polymers, to enhance the suppression of breast cancer proliferation and lung metastasis of TPL. ResultsThe generated TPL/NPs had the high drug loading efficiency (94.93 ± 2.1%) and a desirable average size (191 nm). Mediated by PBAEss core, TPL/NPs displayed a pH/redox dual stimuli drug release profile in vitro. Based on HA coating, TPL/NPs exhibited selective tumor-cellular uptake and high tumor-tissue accumulation capacity via targeting CD44. As a consequence, TPL/NPs showed higher cell proliferation suppression, pro-apoptosis and cell cycle arrest activities, and stronger inhibitory effects on cell migration and invasion than free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and block lung metastasis in a 4T1 breast cancer mice model at equivalent or lower TPL dosage compared to free TPL, with the decreased systemic toxicity. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis, suppressed expression of matrix metalloproteinases, which all these contributed to inhibit tumor growth and pulmonary metastasis. ConclusionCollectively, our results demonstrate that TPL/NPs, which integrates tumor active-targeting and pH/redox responsive drug release, pro-apoptosis, and anti-mobility, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity.

scholarly journals Biotin-streptavidin-guided two-step pretargeting approach using PLGA for molecular ultrasound imaging and chemotherapy for ovarian cancer

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11486
Author(s):  
Hang Zhou ◽  
Jing Fu ◽  
Qihuan Fu ◽  
Yujie Feng ◽  
Ruixia Hong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ultrasound Imaging ◽  
High Performance ◽  
Encapsulation Efficiency ◽  
Plga Nanoparticles ◽  
Cell Counting ◽  
Ovarian Cancer Cells ◽  
Skov3 Cells ◽  
Targeting Ability ◽  
Targeting Strategy

Background Ovarian cancer seriously threatens the lives and health of women, and early diagnosis and treatment are still challenging. Pre-targeting is a promising strategy to improve the treatment efficacy of ovarian cancer and the results of ultrasound imaging. Purpose To explore the effects of a pre-targeting strategy using streptavidin (SA) and paclitaxel (PTX)-loaded phase-shifting poly lactic-co-glycolic acid (PLGA) nanoparticles with perfluoro-n-pentane (PTX-PLGA-SA/PFPs) on the treatment and ultrasound imaging of ovarian cancer. Methods PTX-PLGA/PFPs were prepared with a single emulsion (O/W) solvent evaporation method and SA was attached using carbodiimide. The encapsulation efficiency of PTX and the release characteristics were assessed with high performance liquid chromatography. The phase-change characteristics of the PTX-PLGA-SA/PFPs were investigated. The anti-carcinoembryonic antigen (CEA) antibody (Ab) was covalently attached to PTX-PLGA/PFPs via carbodiimide to create PTX-PLGA-Ab/PFPs. The targeting efficiency of the nanoparticles and the viability of ovarian cancer SKOV3 cells were evaluated in each group using a microscope, flow cytometry, and cell counting kit 8 assays. Results THE PTX-PLGA-SA/PFPs were spheres with a size of 383.0 ± 75.59 nm. The encapsulation efficiency and loading capability of the nanoparticles for PTX were 71.56 ±  6.51% and 6.57 ± 0.61%, respectively. PTX was burst-released up to 70% in 2–3 d. When irradiated at 7.5 W for 3 min, the PTX-PLGA-SA/PFPs visibly enhanced the ultrasonography images (P < 0.05). At temperatures of 45°C and 60°C the nanoparticles phase-shifted into micro-bubbles and the sizes increased. The binding efficiencies of SA and Ab to the PTX-PLGA/PFPs were 97.16 ±  1.20% and 92.74 ± 5.75%, respectively. Pre-targeting resulted in a high binding efficacy and killing effect on SKOV3 cells (P < 0.05). Conclusions The two-step pre-targeting process can significantly enhance the targeting ability of PTX-loaded PLGA nanoparticles for ovarian cancer cells and substantially improve the therapeutic efficacy. This technique provides a new method for ultrasonic imaging and precise chemotherapy for ovarian cancer.

scholarly journals A self-amplified nanocatalytic system for achieving “1 + 1 + 1 > 3” chemodynamic therapy on triple negative breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lulu Zhou ◽  
Jinjin Chen ◽  
Yunhao Sun ◽  
Keke Chai ◽  
Zhounan Zhu ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Parp Inhibitor ◽  
Tumor Therapy ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
In Vivo Studies ◽  
Great Promise ◽  
New Paradigm ◽  
Quinone Oxidoreductase

Abstract Background Chemodynamic therapy (CDT), employing Fenton or Fenton-like catalysts to convert hydrogen peroxide (H2O2) into toxic hydroxyl radicals (·OH) to kill cancer cells, holds great promise in tumor therapy due to its high selectivity. However, the therapeutic effect is significantly limited by insufficient intracellular H2O2 level in tumor cells. Fortunately, β-Lapachone (Lapa) that can exert H2O2-supplementing functionality under the catalysis of nicotinamide adenine dinucleotide (phosphate) NAD(P)H: quinone oxidoreductase-1 (NQO1) enzyme offers a new idea to solve this problem. However, extensive DNA damage caused by high levels of reactive oxygen species can trigger the “hyperactivation” of poly(ADP-ribose) polymerase (PARP), which results in the severe interruption of H2O2 supply and further the reduced efficacy of CDT. Herein, we report a self-amplified nanocatalytic system (ZIF67/Ola/Lapa) to co-deliver the PARP inhibitor Olaparib (Ola) and NQO1-bioactivatable drug Lapa for sustainable H2O2 production and augmented CDT (“1 + 1 + 1 > 3”). Results The effective inhibition of PARP by Ola can synergize Lapa to enhance H2O2 formation due to the continuous NQO1 redox cycling. In turn, the high levels of H2O2 further react with Co2+ to produce the highly toxic ·OH by Fenton-like reaction, dramatically improving CDT. Both in vitro and in vivo studies demonstrate the excellent antitumor activity of ZIF67/Ola/Lapa in NQO1 overexpressed MDA-MB-231 tumor cells. Importantly, the nanocomposite presents minimal systemic toxicity in normal tissues due to the low NQO1 expression. Conclusions This design of nanocatalytic system offers a new paradigm for combing PARP inhibitor, NQO1-bioactivatable drug and Fenton-reagents to obtain sustained H2O2 generation for tumor-specific self-amplified CDT. Graphic Abstract

scholarly journals MAGE-Targeted Gold Nanoparticles for Ultrasound Imaging-Guided Phototherapy in Melanoma

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Xuelin Li ◽  
Shigen Zhong ◽  
Cuncheng Zhang ◽  
Pan Li ◽  
Haitao Ran ◽  
...  
Keyword(s):  
Gas Phase ◽  
Ultrasound Imaging ◽  
Gold Nanorods ◽  
Photothermal Therapy ◽  
Tumor Therapy ◽  
Therapeutic Strategies ◽  
Droplet Vaporization ◽  
Therapy Strategy ◽  
Tunable Optical Properties ◽  
Tumor Area

Gold nanorods exhibit a wide variety of applications such as tumor molecular imaging and photothermal therapy (PTT) due to their tunable optical properties. Several studies have demonstrated that the combination of other therapeutic strategies may improve PTT efficiency. A method called optical droplet vaporization (ODV) was considered as another noninvasive imaging and therapy strategy. Via the ODV method, superheated perfluorocarbon droplets can be vaporized to a gas phase for enhancing ultrasound imaging; meanwhile, this violent process can cause damage to cells and tissue. In addition, active targeting through the functionalization with targeting ligands can effectively increase nanoprobe accumulation in the tumor area, improving the sensitivity and specificity of imaging and therapy. Our study prepared a nanoparticle loaded with gold nanorods and perfluorinated hexane and conjugated to a monoclonal antibody (MAGE-1 antibody) to melanoma-associated antigens (MAGE) targeting melanoma, investigated the synergistic effect of PTT/ODV therapy, and monitored the therapeutic effect using ultrasound. The prepared MAGE-Au-PFH-NPs achieved complete eradication of tumors. Meanwhile, the MAGE-Au-PFH-NPs also possess significant ultrasound imaging signal enhancement, which shows the potential for imaging-guided tumor therapy in the future.

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