Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance

Wang, Hai; Liang, Yutong; Yin, Yue; Zhang, Jie; Su, Wen; White, Alisa; Jiang, Bin; Xu, Jiangsheng; Zhang, Yuntian; Stewart, Stanford J.; Lu, Xiongbin; He, Xiaoming

doi:10.1038/s41467-020-20588-0

Cited by 60 publications

(50 citation statements)

References 51 publications

(53 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ATP from the mitochondria contributes to the overexpression of drug efflux pumps to induce MDR, suggesting that damage of the mitochondria and a reduction in ATP levels can effectively reverse drug resistance [ 37 ]. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer

et al. 2021

View full text Add to dashboard Cite

Background Mitochondria play a role in the occurrence, development, drug resistance, metastasis, and other functions of cancer and thus are a drug target. An acid-activated mitochondria-targeting drug nanocarrier with redox-responsive function was constructed in the present study. However, whether this vector can precisely delivery paclitaxel (PTX) to enhance therapeutic efficacy in drug-resistant lung cancer is unknown. Results Acid-cleavable dimethylmaleic anhydride (DA) was used to modify pluronic P85-conjugated mitochondria-targeting triphenylphosphonium (TPP) using disulfide bonds as intermediate linkers (DA-P85-SS-TPP and DA-P-SS-T). The constructed nanocarriers demonstrated enhanced cellular uptake and selective mitochondrial targeting at extracellular pH characteristic for a tumor (6.5) and were characterized by extended circulation in the blood. TPP promoted the targeting of the DA-P-SS-T/PTX nanomicelles to the mitochondrial outer membrane to decrease the membrane potential and ATP level, resulting in inhibition of P-glycoprotein and suppression of drug resistance and cancer metastasis. PTX was also rapidly released in the presence of high glutathione (GSH) levels and directly diffused into the mitochondria, resulting in apoptosis of drug-resistant lung cancer cells. Conclusions These promising results indicated that acid-activated mitochondria-targeting and redox-responsive nanomicelles potentially represent a significant advancement in cancer treatment. Graphic Abstarct

show abstract

Section: Resultsmentioning

confidence: 99%

pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Nanoparticles have also been exploited as carriers for therapeutics that can modulate the expression and activity of membrane transporters [ 106 , 107 ]. Many of these studies have involved the delivery of nucleic acids such as small interfering RNA (siRNA) and antisense oligonucleotides, which are ideal candidates for nanoencapsulation since this can protect against premature degradation by nucleases in the circulation [ 108 ].…”

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

View full text Add to dashboard Cite

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.

show abstract

“…Wang et al . coated carbon‐based ‘nano‐onions’ with fucoidan to improve their solubility and stability, and the resultant system could specially target tumor vasculature 53 . Meanwhile, the bioavailability of some anticancer drugs is greatly reduced due to their inherent low solubility and physical instability in clinical application 54 .…”

Section: The Use Of Biomacromolecules In Nano‐assemblies To Overcome ...mentioning

confidence: 99%

Nano‐assemblies based on biomacromolecules to overcome cancer drug resistance

Cheng

Dou

2021

Polymer International

View full text Add to dashboard Cite

Overcoming tumor resistance is one of the major challenges encountered in cancer treatment. With the rapid development of nanotechnology in recent years, nano‐assemblies have become promising candidates due to their strong potential to overcome the drug resistance of tumors. They have a high degree of adaptability, including size and composition regulation, surface versatility and the possibility of combining multiple therapeutic approaches through a single nanoparticle platform. Among multiple self‐assembled component materials, biomacromolecules have attracted ever growing attention because of their unique molecular structures, natural biocompatibility and multifunctional properties. Herein, various mechanisms of nano‐assembly utilization overcoming cancer drug resistance are first summarized, and then the roles and research progress of typical biomacromolecules (such as polysaccharides, proteins and nucleic acids) in nano‐assemblies capable of overcoming cancer drug resistance are described. Finally, the potential challenges and prospects of the clinical application of biomacromolecule‐based nano‐assemblies are analyzed and discussed. © 2021 Society of Industrial Chemistry.

show abstract

Carbon nano-onion-mediated dual targeting of P-selectin and P-glycoprotein to overcome cancer drug resistance

Cited by 60 publications

References 51 publications

pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer

pH-activated, mitochondria-targeted, and redox-responsive delivery of paclitaxel nanomicelles to overcome drug resistance and suppress metastasis in lung cancer

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

Nano‐assemblies based on biomacromolecules to overcome cancer drug resistance

Contact Info

Product

Resources

About