Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer

Debele, Tilahun Ayane; Wu, Hao; Wu, Shang; Shan, Yan Shen; Su, Wen

doi:10.3390/pharmaceutics12080778

Cited by 15 publications

(11 citation statements)

References 42 publications

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“…In comparison to free drugs, nanoformulated drugs show different anticancer activity in the in vitro experiments which may be due to the drug release mechanism or their direct interaction with the cell of interest [ 39 ]. Hence, to study the in vitro cytotoxicity effect of the AUY922-loaded micelle, free AUY922, PLGA-Cys, and HA-SS-PLGA in the cellular proliferation of cancer cells, cell viability was evaluated by the MTT assay using brain cancer cells (i.e., U87, P5, and P5-TMZ-R).…”

Section: Resultsmentioning

confidence: 99%

“…The GSH-sensitive hyaluronic acid derivative (HA-SS-PLGA) was synthesized using two separate reaction steps, as shown in Scheme 1 . First, the carboxyl group of PLGA was activated with EDC/NHS and then one of the amine groups of cystamine reacted with the activated carboxyl group of PLGA to form PLGA-Cys (detailed synthesis protocols were mentioned in our previous paper) [ 39 ]. In the second reaction step, the carboxyl group of HA was activated in the presence of EDC/NHS and conjugated with the PLGA-Cys to form HA-SS-PLGA copolymer.…”

Section: Experimental Methodsmentioning

confidence: 99%

“…The micelle containing drugs was synthesized using the emulsion solvent evaporation method [ 39 , 40 ]. Briefly, HA-SS-PLGA and/or TF-HA-SS-PLGA (20 mg each) and AUY922 (10 mg) were dissolved in dichloromethane (10 mL) under stirring until a clear homogenous solution was obtained.…”

Section: Experimental Methodsmentioning

confidence: 99%

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Transferrin Modified GSH Sensitive Hyaluronic Acid Derivative Micelle to Deliver HSP90 Inhibitors to Enhance the Therapeutic Efficacy of Brain Cancers

Debele

Wei

et al. 2021

Cancers

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Herein, GSH-sensitive hyaluronic acid-poly(lactic-co-glycolic acid) (HA-SS-PLGA) was synthesized. Surface modification of PLGA with hyaluronic acid produced a highly stable micelle at physiological pH while a micelle was destabilized at a higher GSH level. Fluorescence microscopy results showed that rhodamine-encapsulated micelle was taken up by brain cancer cells, while competitive inhibition was observed in the presence of free HA and free transferrin. In vitro cytotoxicity results revealed that transferrin-targeted nanoformulated AUY922 (TF-NP-AUY922) shows higher cytotoxicity than either free AUY922 or non-targeted AUY922-loaded micelles (NP-AUY922). In comparison to the control groups, free AUY922, TF-NP-AUY922 or NP-AUY922 treatment revealed the upregulation of HSP70, while the expression of HSP90 client proteins was simultaneously depleted. In addition, the treatment group induced caspase-dependent PARP cleavage and the upregulation of p53 expression, which plays a key role in apoptosis of brain cancer cells. In vivo and ex vivo biodistribution studies showed that cypate-loaded micelle was taken up and accumulated in the tumor regions. Furthermore, in vivo therapeutic efficacy studies revealed that the AUY922-loaded micelle significantly suppressed tumor growth in comparison to the free AUY922, or control groups using tumor-bearing NOD-SCID mice. Moreover, biochemical index and histological analysis revealed synthesized micelle does not show any significant cytotoxicity to the selected major organs. Overall, a synthesized micelle is the best carrier for AUY922 to enhance the therapeutic efficiency of brain cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Experimental Methodsmentioning

confidence: 99%

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Transferrin Modified GSH Sensitive Hyaluronic Acid Derivative Micelle to Deliver HSP90 Inhibitors to Enhance the Therapeutic Efficacy of Brain Cancers

Debele

Wei

et al. 2021

Cancers

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“…The calculated CI values were observed to be less than one, which indicates a stronger synergistic effect for the nanoformulated drugs (PAH-SS-PLGA-TOS-curcumin) on cellular proliferation. Thus, it can be concluded that the selected drugs in combination can pave the way for enhancing the therapeutic efficacy and act as a treatment option for pancreatic cancer (Debele et al, 2020 ).…”

Section: Combination Based Onconanotherapeuticsmentioning

confidence: 99%

A technical note on emerging combination approach involved in the onconanotherapeutics

Iqubal

Kaur

et al. 2022

Drug Delivery

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Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the exploratory preclinical and clinical studies, it was found that therapeutic response increases multiple folds when anticancer drugs are used in combination. However, the conventional combination of anticancer drugs was associated with various limitations such as increased cost of treatment, systemic toxicity, drug resistance, and reduced pharmacokinetic attributes. Hence, attempts were made to formulate nanocarrier fabricated combinatorial drugs (NFCDs) to effectively manage and treat cancer. This approach offers several advantages, such as improved stability, lower drug exposure, targeted drug delivery, low side effects, and improved clinical outcome. Hence, in this review, first time, we have discussed the recent advancement and various types of nano carrier-based combinatorial drug delivery systems in a different type of cancer and highlighted the personalized combinatorial theranostic medicine as a futuristic anticancer treatment approach.

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“…Taken together, nanotechnology can clearly help to offset resistance either by correcting physiological alterations in tumours, or by exploiting them for on-demand drug release. Aside from pH and oxygen status, interest in other tumour features, such as elevated glutathione levels, has also produced encouraging results that are worthy of further investigation [ 223 , 224 , 225 , 226 , 227 ].…”

Section: Addressing Therapy Resistance In Paca Using Nanoparticle-based Platformsmentioning

confidence: 99%

Nanomedicine in Pancreatic Cancer: Current Status and Future Opportunities for Overcoming Therapy Resistance

Greene

Johnston

Scott

2021

Cancers

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The development of drug resistance remains one of the greatest clinical oncology challenges that can radically dampen the prospect of achieving complete and durable tumour control. Efforts to mitigate drug resistance are therefore of utmost importance, and nanotechnology is rapidly emerging for its potential to overcome such issues. Studies have showcased the ability of nanomedicines to bypass drug efflux pumps, counteract immune suppression, serve as radioenhancers, correct metabolic disturbances and elicit numerous other effects that collectively alleviate various mechanisms of tumour resistance. Much of this progress can be attributed to the remarkable benefits that nanoparticles offer as drug delivery vehicles, such as improvements in pharmacokinetics, protection against degradation and spatiotemporally controlled release kinetics. These attributes provide scope for precision targeting of drugs to tumours that can enhance sensitivity to treatment and have formed the basis for the successful clinical translation of multiple nanoformulations to date. In this review, we focus on the longstanding reputation of pancreatic cancer as one of the most difficult-to-treat malignancies where resistance plays a dominant role in therapy failure. We outline the mechanisms that contribute to the treatment-refractory nature of these tumours, and how they may be effectively addressed by harnessing the unique capabilities of nanomedicines. Moreover, we include a brief perspective on the likely future direction of nanotechnology in pancreatic cancer, discussing how efforts to develop multidrug formulations will guide the field further towards a therapeutic solution for these highly intractable tumours.

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Combination Delivery of Alpha-Tocopheryl Succinate and Curcumin Using a GSH-Sensitive Micelle (PAH-SS-PLGA) to Treat Pancreatic Cancer

Cited by 15 publications

References 42 publications

Transferrin Modified GSH Sensitive Hyaluronic Acid Derivative Micelle to Deliver HSP90 Inhibitors to Enhance the Therapeutic Efficacy of Brain Cancers

Transferrin Modified GSH Sensitive Hyaluronic Acid Derivative Micelle to Deliver HSP90 Inhibitors to Enhance the Therapeutic Efficacy of Brain Cancers

A technical note on emerging combination approach involved in the onconanotherapeutics

Nanomedicine in Pancreatic Cancer: Current Status and Future Opportunities for Overcoming Therapy Resistance

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