Epirubicin-loaded polymeric micelles effectively treat axillary lymph nodes metastasis of breast cancer through selective accumulation and pH-triggered drug release

Chida, Tsukasa; Miura, Yutaka; Cabral, Horacio; Nomoto, Takahiro; Kataoka, Kazunori; Nishiyama, Nobuhiro

doi:10.1016/j.jconrel.2018.10.035

Cited by 56 publications

(33 citation statements)

References 54 publications

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“…They are made of a single layer, and hydrophobic drugs can be carried in the core of micelles. Chida et al used epirubicin-loaded micelles made of poly(ethylene glycol)-bpoly(beta-benzyl L aspartate) to target breast cancer metastases in the axillary lymph nodes [145]. Epirubicin polymeric micelles had pH-triggered drug release and inhibited tumor growth and metastasis to the axillary lymph nodes.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

Cote

Rao

Alany

et al. 2019

Advanced Drug Delivery Reviews

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Although many solid tumors use the lymphatic system to metastasize, there are few treatment options that directly target cancer present in the lymphatic system, and those that do are highly invasive, uncomfortable, and/or have limitations. This review gives a brief overview of lymphatic function and anatomy, discusses changes that befall the lymphatics in cancer and the mechanisms by which these changes occur, and presents limitations for drug delivery to the lymphatic system. We then go on to summarize relevant techniques and new research for targeting cancer populations in the lymphatics and enhancing drug delivery intralymphatically, including intralymphatic injections, isolated limb perfusion, passive nano drug delivery systems, and actively targeted nanomedicine.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

Cote

Rao

Alany

et al. 2019

Advanced Drug Delivery Reviews

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“…Stimuli‐responsive polymeric micelles can control the drug release rate by adjusting the interaction of the drug with the core‐forming segment of the block copolymers. [ 7b,9,190 ] The pH‐sensitive NC‐6300 elicit selective drug release of Epi at intratumoral pH, [ 82 ] showing enhanced activity and less side effects than conventional epirubicin formulations in clinical studies. [ 83,84 ] Indeed, the recommended dose for the phase II studies is higher than the standard dose of Epi (170 and 50–120 mg m −2 , respectively).…”

Section: Analysis Of the Preclinical And Clinical Results Of Self‐assmentioning

confidence: 99%

“…Furthermore, according to a recent preclinical study, NC‐6300 could selectively accumulate and penetrate into both primary breast cancer and the axillary lymph node metastasis (ALNM), leading to effective suppression of ALNM caused by triple negative breast cancer (TNBC). [ 82 ]…”

Section: Self‐assembled Cancer Nanomedicines In Preclinical and Clinimentioning

confidence: 99%

Clinical Translation of Self‐Assembled Cancer Nanomedicines

Miyata

Kataoka

et al. 2020

Advanced Therapeutics

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Nanomedicines are emerging as effective approaches for developing new strategies against cancer. Nanomedicines can be designed for selectively delivering probes and anticancer agents to tumors for achieving improved diagnostic or therapeutic efficacy, while relieving potential side effects. In particular, the number of formulations based on self‐assembled nanostructures under clinical evaluation is increasing due to their unique advantages for elegant and facile preparation, working at the biointerface and spatiotemporally controlling the function of drugs. Here, the current status of clinically used self‐assembled nanomedicines is presented, and recent advances of candidates in clinical trials are reviewed. In addition, the challenges and future prospects of nanomedicines in the clinic are discussed.

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“…The hypothesis that ROS might attack from the extracellular matrix is one of the possible causes of this combination treatment. NC-6300 is moved from blood vessel to tumor region by EPR effect and may be first accumulated in the extracellular matrix (Chida et al, 2018). We assume that some intervention of ROS could occur from extracellular matrix to membrane (Supplementary Figure S3).…”

Section: Discussionmentioning

confidence: 99%

Function of Epirubicin-Conjugated Polymeric Micelles in Sonodynamic Therapy

et al. 2019

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The combinatory use of high-intensity focused ultrasound (HIFU) and epirubicin (EPI)-conjugated polymeric micellar nanoparticles (NC-6300) is thought to be a less invasive and more efficient method of cancer therapy. To investigate the mechanism underlying the combination effect, we examined the effect of trigger-pulsed HIFU (TP-HIFU) and NC-6300 from the perspective of reactive oxygen species (ROS) generation, which is considered the primary function of sonodynamic therapy (SDT), and changes in drug characteristics. TP-HIFU is an effective sequence for generating hydroxyl radicals to kill cancer cells. EPI was susceptible to degradation by TP-HIFU through the production of hydroxyl radicals. In contrast, EPI degradation of NC-6300 was suppressed by the hydrophilic shell of the micelles. NC-6300 also exhibited a sonosensitizer function, which promoted the generation of superoxide anions by TP-HIFU irradiation. The amount of ROS produced by TP-HIFU reached a level that caused structural changes to the cellular membrane. In conclusion, drug-conjugated micellar nanoparticles are more desirable for SDT because of accelerated ROS production and drug protection from ROS. Furthermore, a combination of NC-6300 and TP-HIFU is useful for minimally invasive cancer therapy with cooperative effects of HIFU-derived features, antitumor activity of EPI, and increased ROS generation to cause damage to cancer cells.

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Epirubicin-loaded polymeric micelles effectively treat axillary lymph nodes metastasis of breast cancer through selective accumulation and pH-triggered drug release

Cited by 56 publications

References 54 publications

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

Lymphatic changes in cancer and drug delivery to the lymphatics in solid tumors

Clinical Translation of Self‐Assembled Cancer Nanomedicines

Function of Epirubicin-Conjugated Polymeric Micelles in Sonodynamic Therapy

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