Development and mechanistic insight into enhanced cytotoxic potential of hyaluronic acid conjugated nanoparticles in CD44 overexpressing cancer cells

Saneja, Ankit; Nayak, Debasis; Srinivas, M.; Kumar, Amit; Khare, Vaibhav; Katoch, Archana; Goswami, Anindya; Vishwakarma, Ram A.; Sawant, Sanghapal D.; Gupta, Prem N.

doi:10.1016/j.ejps.2016.10.028

Cited by 34 publications

(25 citation statements)

References 53 publications

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“…For example, IC87114 loaded polymeric NPs modified by HA with average size of 200 nm and ZP of -10 mV, exhibited higher uptake into MDA-MB-231 with moderate CD44 expression (189). In another study, NPs composed of HA-HPCD/ADA-PEG (HA: hyaluronic acid, HPCD: HP-βcyclodextrin, ADA: 1-adamantane carboxylic acid) with negative ZP (−14 mV) were delivered into A549 cells successfully (181).…”

Section: Importance Of Zp In Active Targeting Of Nps Into Cancer Cellsmentioning

confidence: 99%

Drug Targeting Strategies Based on Charge Dependent Uptake of Nanoparticles into Cancer Cells

et al. 2019

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The aim of this review was to describe the preferred charged nano-particles (CNPs) for targeted delivery in tumor cells. Zeta Potential (ZP), which represents the surface charge of NPs was highlighted in cell entrance and interactions. In this regard, various types of endocytosis pathways which are involved in NPs’ uptake were first introduced. Then, significance of positively charged NPs (PCNPs) in proton sponge effect corresponding to lysosomal escape was discussed. Cells prefer to endocyte the NPs with positive charge in passive targeting and gene delivery, while in active targeting; the charge of receptors’ ligand binding site determines the NPs cellular uptake. Moreover, pH-sensitive NPs represent charge reversible behavior depending on pH changes which leads to longer blood circulation residence and higher uptake at acidic microenvironment of the cancer media. Role of the CNPs in overcoming multidrug resistance (MDR) and bypassing p-glycoprotein was further investigated.

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Section: Importance Of Zp In Active Targeting Of Nps Into Cancer Cellsmentioning

confidence: 99%

Drug Targeting Strategies Based on Charge Dependent Uptake of Nanoparticles into Cancer Cells

et al. 2019

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“…22,23 Furthermore, HA possesses many advantages such as being nontoxic, noninflammatory, biocompatible, and biodegradable when it is used as a moiety for anticancer drug delivery. 24,25 In summary, an ideal delivery system would be the combination of HA active targeting and VES-based redox-sensitive nanocarriers in that a multifunctional carrier is capable of binding HA receptor-mediated active targeting, followed by stimuli-triggered release and VES-based nanotechnology as shown in Figure 1A, which will further enhance their effectiveness. Here, we report a novel redox-sensitive nanocarrier consisting of HA as a hydrophilic segment, a redox-sensitive connecting bridge containing one disulfide group, and VES as a hydrophobic segment (HA-SS-VES, HSV).…”

Section: Introductionmentioning

confidence: 99%

Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin E succinate conjugates for improved lung cancer treatment

Song

Cai

Yin

et al. 2018

IJN

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BackgroundLung cancer is the primary cause of cancer-related death worldwide. A redox-sensitive nanocarrier system was developed for tumor-targeted drug delivery and sufficient drug release of the chemotherapeutic agent paclitaxel (PTX) for improved lung cancer treatment.MethodsThe redox-sensitive nanocarrier system constructed from a hyaluronic acid-disulfide-vitamin E succinate (HA-SS-VES, HSV) conjugate was synthesized and PTX was loaded in the delivery system. The physicochemical properties of the HSV nanoparticles were characterized. The redox-sensitivity, tumor-targeting and intracellular drug release capability of the HSV nanoparticles were evaluated. Furthermore, in vitro and in vivo antitumor activity of the PTX-loaded HSV nanoparticles was investigated in a CD44 over-expressed A549 tumor model.ResultsThis HSV conjugate was successfully synthesized and self-assembled to form nanoparticles in aqueous condition with a low critical micelle concentration of 36.3 μg mL−1. Free PTX was successfully entrapped into the HSV nanoparticles with a high drug loading of 33.5% (w/w) and an entrapment efficiency of 90.6%. Moreover, the redox-sensitivity of the HSV nanoparticles was confirmed by particle size change of the nanoparticles along with in vitro release profiles in different reducing environment. In addition, the HA-receptor mediated endocytosis and the potency of redox-sensitivity for intracellular drug delivery were further verified by flow cytometry and confocal laser scanning microscopic analysis. The antitumor activity results showed that compared to redox-insensitive nanoparticles and Taxol®, PTX-loaded redox-sensitive nanoparticles exhibited much greater in vitro cytotoxicity and apoptosis-inducing ability against CD44 over-expressed A549 tumor cells. In vivo, the PTX-loaded HSV nanoparticles possessed much higher antitumor efficacy in an A549 mouse xenograft model and demonstrated improved safety profile. In summary, our PTX-loaded redox-sensitive HSV nanoparticles demonstrated enhanced antitumor efficacy and improved safety of PTX.ConclusionThe results of our study indicated the redox-sensitive HSV nanoparticle was a promising nanocarrier for lung cancer therapy.

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“…Interestingly, as shown in Figure 10A, there was no significant difference between cells incubated with DOX⋅HCl and DOX-loaded micelles for 4 h. However, after 24 h incubation, DOX fluorescence was stronger in the cells of the DOX-loaded micelles group than in the DOX⋅HCl group ( Figure 10B). This was probably because DOX⋅HCl diffused into the cells through passive diffusion without a release process and DOX-loaded micelles were internalized by the cells via a CD44 receptor-mediated endocytosis mechanism with a reduction-triggered release process, 62 which delayed the release of DOX in the first 4 h. The result demonstrated that the micelles effectively enhanced the cellular uptake of DOX-loaded micelles within 24 h. The fluorescent intensity of DOX in HCCLM3 cells was calculated by the LAS AF software. As shown in Figure 10C, compared with DOX⋅HCl, the uptake of HA-ss-FA/DOX increased 15.81% after 24 h incubation (P,0.05).…”

Section: In Vitro Cytotoxicity Testsmentioning

confidence: 99%

Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery

Yang¹,

Lan²,

Kang³

et al. 2018

IJN

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IntroductionA reduction-sensitive CD44-positive tumor-targetable drug delivery system for doxorubicin (DOX) delivery was developed based on hyaluronic acid (HA)-grafted polymers.Materials and methodsHA was conjugated with folic acid (FA) via a reduction-sensitive disulfide linkage to form an amphiphilic polymer (HA-ss-FA). The chemical structure of HA-ss-FA was analyzed by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of HA-ss-FA was determined by high-performance gel permeation chromatography. Blank HA-ss-FA micelles and DOX-loaded micelles were prepared and characterized. The reduction responsibility, cellular uptake, and in vivo biodistribution of HA-ss-FA micelles were investigated.ResultsDOX-loaded micelles were of high encapsulation efficiency (88.09%), high drug-loading content (22.70%), appropriate mean diameter (100–120 nm), narrow size distribution, and negative zeta potential (−6.7 to −31.5 mV). The DOX release from the micelles was significantly enhanced in reduction environment compared to normal environment. The result of in vitro cytotoxicity assay indicated that the blank micelles were of low toxicity and good biocompatibility and the cell viabilities were >100% with the concentration of HA-ss-FA from 18.75 to 600.00 μg/mL. Cellular uptake and in vivo biodistribution studies showed that DOX-loaded micelles were tumor-targetable and could significantly enhance cellular uptake by CD44 receptor-mediated endocytosis, and the cellular uptake of DOX in CD44-positve A549 cells was 1.6-fold more than that in CD44-negative L02 cells. In vivo biodistribution of HA-ss-FA micelles showed that micelles were of good in vivo tumor targetability and the fluorescence of indocyanine green (ICG)-loaded micelles was 4- to 6.6-fold stronger than free ICG within 6 h in HCCLM3 tumor-bearing nude mice.ConclusionHA-ss-FA is a promising nanocarrier with excellent biocompatibility, tumor targetability, and controlled drug release capability for delivery of chemotherapy drugs in cancer therapy.

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Development and mechanistic insight into enhanced cytotoxic potential of hyaluronic acid conjugated nanoparticles in CD44 overexpressing cancer cells

Cited by 34 publications

References 53 publications

Drug Targeting Strategies Based on Charge Dependent Uptake of Nanoparticles into Cancer Cells

Drug Targeting Strategies Based on Charge Dependent Uptake of Nanoparticles into Cancer Cells

Paclitaxel-loaded redox-sensitive nanoparticles based on hyaluronic acid-vitamin E succinate conjugates for improved lung cancer treatment

Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery

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