CD44-specific nanoparticles for redox-triggered reactive oxygen species production and doxorubicin release

Lin, Chun-Yu; Lu, Kun Ying; Wang, Sin Yu; Sung, Hsing‐Wen; Mi, Fwu Long

doi:10.1016/j.actbio.2016.02.005

Cited by 38 publications

(16 citation statements)

References 43 publications

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“…Similarly, Hou et al ( 2016 ) fabricated HA-modified single-walled carbon nanotubes wherein the HA was further conjugated to DOX by disulphide bonds making the nano-chemotherapeutics sensitive to redox potential. Whereas, Lin et al ( 2016 ) developed bioreducible DOX-loaded chitosan-based nano-chemotherapeutics with HA for production of intracellular glutathione-triggered reactive oxygen species and simultaneous release of chemotherapeutics. Shi et al ( 2014 ) developed DOX-loaded star-shaped micellar system made up of amphiphilic co-polymer crosslinked with phenylboronic acid-functionalized reduction-sensitive amphiphilic co-polymer having tumor targeting ability.…”

Section: Types Of Nanocarriersmentioning

confidence: 99%

Tumor Microenvironment Targeted Nanotherapy

2018

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Recent developments in nanotechnology have brought new approaches to cancer diagnosis and therapy. While enhanced permeability and retention effect promotes nano-chemotherapeutics extravasation, the abnormal tumor vasculature, high interstitial pressure and dense stroma structure limit homogeneous intratumoral distribution of nano-chemotherapeutics and compromise their imaging and therapeutic effect. Moreover, heterogeneous distribution of nano-chemotherapeutics in non-tumor-stroma cells damages the non-tumor cells, and interferes with tumor-stroma crosstalk. This can lead not only to inhibition of tumor progression, but can also paradoxically induce acquired resistance and facilitate tumor cell proliferation and metastasis. Overall, the tumor microenvironment plays a vital role in regulating nano-chemotherapeutics distribution and their biological effects. In this review, the barriers in tumor microenvironment, its consequential effects on nano-chemotherapeutics, considerations to improve nano-chemotherapeutics delivery and combinatory strategies to overcome acquired resistance induced by tumor microenvironment have been summarized. The various strategies viz., nanotechnology based approach as well as ligand-mediated, redox-responsive, and enzyme-mediated based combinatorial nanoapproaches have been discussed in this review.

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Section: Types Of Nanocarriersmentioning

confidence: 99%

Tumor Microenvironment Targeted Nanotherapy

2018

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“…DCFDA is deacetylated by esterases to dichlorofluorescein (DCFH) and subsequently reacts with ROS to generate the green fluorophore, DCF. 52 MIA PaCa-2R cells were seeded in 12-well plates for 24 h and incubated with free volasertib and micelles carrying ether miR-34a, volasertib, or their combination. The concentrations of volasertib and miR-34a were fixed at 50 and 100 nM.…”

Section: Methodsmentioning

confidence: 99%

ROS-Responsive Polymeric Micelles for Triggered Simultaneous Delivery of PLK1 Inhibitor/miR-34a and Effective Synergistic Therapy in Pancreatic Cancer

Xin

Lin

Wang

et al. 2019

ACS Appl. Mater. Interfaces

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Ineffective drug delivery and poor prognosis are two major challenges in the treatment of pancreatic ductal adenocarcinoma (PDAC). While there is significant downregulation of tumor suppressor microRNA-34a (miR-34a), which targets many oncogenes related to proliferation, apoptosis, and invasion, high expression level of Polo-like kinase 1 (PLK1) is closely associated with short survival rates of pancreatic cancer patients. Therefore, the objective is to codeliver miR-34a mimic and small molecule PLK1 inhibitor volasertib (BI6727) using poly(ethylene glycol)–poly[aspartamidoethyl(p-boronobenzyl)diethylammonium bromide] (PEG-B-PAEBEA). This polymer could self-assemble into micelles of ~100 nm with 10% drug loading of volasertib and form a complex with miR-34a at the N/P ratio of 18 and higher. Combination treatment of volasertib and miR-34a displayed the synergistic effect and superior antiproliferative activity along with an enhanced G2/M phase arrest and suppression of colony formation, leading to cell death due to potential c-myc targeting therapeutics. Orthotopic pancreatic tumor bearing NSG mice were scanned for fluorescence by IVIS after systemic administration of micelles encapsulating volasertib and miR-34a at doses of 5 and 1 mg/kg, respectively. Cy5.5 concentration in plasma and major organs was determined by measuring fluorescence intensity. There was significant reduction in tumor volume, and histological examination of major organs suggested negligible systemic toxicity. In conclusion, PEG-B-PAEBEA micelles carrying volasertib and miR-34a mimic have the potential to treat pancreatic cancer.

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“…Progress on redox-responsive Ms-DDS has been described previously 18 . Also, disulfide bond-based redox-responsive Ms-DDS have been utilized in several nanocarriers, such as zwitterionic dextran nanoparticles 31 , single-walled carbon nanotubes 32 , chitosan-based nanoparticles 33 , PEGylation micelles 34 , and mesoporous silica nanoparticles 35 , 36 . These redox-sensitive Ms-DDS should be designed carefully to make them not only stable in the blood circulation but also in the tumor tissue before entering into tumor cells.…”

Section: Tumor Microenvironment and Cellular Biological Stimulimentioning

confidence: 99%

Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment

et al. 2017

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The development of traditional tumor-targeted drug delivery systems based on EPR effect and receptor-mediated endocytosis is very challenging probably because of the biological complexity of tumors as well as the limitations in the design of the functional nano-sized delivery systems. Recently, multistage drug delivery systems (Ms-DDS) triggered by various specific tumor microenvironment stimuli have emerged for tumor therapy and imaging. In response to the differences in the physiological blood circulation, tumor microenvironment, and intracellular environment, Ms-DDS can change their physicochemical properties (such as size, hydrophobicity, or zeta potential) to achieve deeper tumor penetration, enhanced cellular uptake, timely drug release, as well as effective endosomal escape. Based on these mechanisms, Ms-DDS could deliver maximum quantity of drugs to the therapeutic targets including tumor tissues, cells, and subcellular organelles and eventually exhibit the highest therapeutic efficacy. In this review, we expatiate on various responsive modes triggered by the tumor microenvironment stimuli, introduce recent advances in multistage nanoparticle systems, especially the multi-stimuli responsive delivery systems, and discuss their functions, effects, and prospects.

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CD44-specific nanoparticles for redox-triggered reactive oxygen species production and doxorubicin release

Cited by 38 publications

References 43 publications

Tumor Microenvironment Targeted Nanotherapy

Tumor Microenvironment Targeted Nanotherapy

ROS-Responsive Polymeric Micelles for Triggered Simultaneous Delivery of PLK1 Inhibitor/miR-34a and Effective Synergistic Therapy in Pancreatic Cancer

Current Multistage Drug Delivery Systems Based on the Tumor Microenvironment

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