Overcoming the polyethylene glycol dilemma via pathological environment-sensitive change of the surface property of nanoparticles for cellular entry

Hama, Susumu; Itakura, Shoko; Nakai, Mayumi; Nakayama, Kayoko; Morimoto, Satoshi; Suzuki, Satoko; Kogure, Kentaro

doi:10.1016/j.jconrel.2015.03.011

Cited by 93 publications

(78 citation statements)

References 28 publications

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“…8 This because PEGylation of such nanosystems allows reaching of a tumor by the EPR effect, but at the same time the hydrophilic shell obstructs an optimal and fast uptake by cancer cells within the tumor thus releasing the payload into the tumor milieu rather than within cancer cells (PEG dilemma). 9,10 On the other hand, notwithstanding that polymeric supramolecular nano-sized aggregates provide an excellent platform to specically deliver anticancer agents, their thermodynamic instability in physiological medium can drastically decrease the therapeutic efficacy.…”

Section: 4-6mentioning

confidence: 99%

Polyaminoacid–doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy

et al. 2016

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An amphiphilic copolymer carrying high-dose doxorubicin (21% on a weight basis), PHEA-EDA-P,C-Doxo, was prepared by coupling doxorubicin with a biocompatible polyaminoacid through a pH-sensitive spacer.Additional derivatization with 4-pentynoic acid endows it with self-assembling properties by means of p-p stacking. These micelles can be triggered to promptly release drug in lysosomes ($40% in 12 h) through pHdependent micelle hydrolysis after uptake. In vitro tests on co-cultures of cancer (MDA-MB 231) and normal (HB-2) breast cells proved that the conjugate was selectively internalized into the former rather than normal cells, exploiting the caveolae-dependent endocytosis pathway, explaining the selective cytotoxic effect toward cancer cells. Intracellular trafficking study of MDA-MB 231 showed that the delivery of the endocytosed drug occurs through the direct fusion of caveosomes with late lysosomes, triggering a massive release in the cytoplasm, bringing about cell death. Dose-effectiveness and mechanistic data indicate that PHEA-EDA-P,C-Doxo is endowed with a distinctive combination of selectivity and pharmacological potency (EC50 13 mM, E max ¼ 77% and EC50 > 25 mM, E max ¼ 21% for cancer and healthy cells respectively) that makes it an excellent candidate for future preclinical studies.

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Section: 4-6mentioning

confidence: 99%

Polyaminoacid–doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy

et al. 2016

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“…The resulting surface charge-reversible vehicles had higher tumor accumulation of fluorescent dye-labeled siRNA than non-charge-reversible negative and positive control vehicles. A similar surface charge-conversional vehicle was also developed using peptides comprising histidine and glutamic acid residues[145] [Fig. 5B].…”

mentioning

confidence: 99%

Recent progress in development of siRNA delivery vehicles for cancer therapy

Kim

Miyata

et al. 2016

Advanced Drug Delivery Reviews

375

305

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Recent progress in RNA biology has broadened the scope of therapeutic targets of RNA drugs for cancer therapy. However, RNA drugs, typically small interfering RNAs (siRNAs), are rapidly degraded by RNases and filtrated in the kidney, thereby requiring a delivery vehicle for efficient transport to the target cells. To date, various delivery formulations have been developed from cationic lipids, polymers, and/or inorganic nanoparticles for systemic delivery of siRNA to solid tumors. This review describes the current status of clinical trials related to siRNA-based cancer therapy, as well as the remaining issues that need to be overcome to establish a successful therapy. It, then introduces various promising design strategies of delivery vehicles for stable and targeted siRNA delivery, including the prospects for future design.

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“…This might on the one hand enhance the colloidal stability of the liposomes but, on the other hand, decrease their cellular uptake due to steric repulsions. 35 Nevertheless, in the case of active targeting, such a negative charge might be even beneficial as it could potentially decrease nonspecific interactions between liposomes and cells. The ICG absorbance signal in liposomes remained stable even after 48-hour incubation in 50% FBS, and the liposome size distribution was not dramatically affected as well.…”

mentioning

confidence: 99%

Photoacoustic imaging of tumor targeting with riboflavin-functionalized theranostic nanocarriers

Beztsinna

Tsvetkova

Jose

et al. 2017

IJN

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Photoacoustic imaging is an emerging method in the molecular imaging field, providing high spatiotemporal resolution and sufficient imaging depths for many clinical applications. Therefore, the aim of this study was to use photoacoustic imaging as a tool to evaluate a riboflavin (RF)-based targeted nanoplatform. RF is internalized by the cells through a specific pathway, and its derivatives were recently shown as promising tumor-targeting vectors for the drug delivery systems. Here, the RF amphiphile synthesized from a PEGylated phospholipid was successfully inserted into a long-circulating liposome formulation labeled with the clinically approved photoacoustic contrast agent – indocyanine green (ICG). The obtained liposomes had a diameter of 124 nm (polydispersity index =0.17) and had a negative zeta potential of −26 mV. Studies in biological phantoms indicated a stable and concentration-dependent photoacoustic signal (Vevo ® LAZR) of the ICG-containing RF-functionalized liposomes. In A431 cells, a high uptake of RF-functionalized liposomes was found and could be blocked competitively. First, studies in mice revealed ~3 times higher photoacoustic signal in subcutaneous A431 tumor xenografts ( P <0.05) after injection of RF-functionalized liposomes compared to control particles. In this context, the application of a spectral unmixing protocol confirmed the initial quantitative data and improved the localization of liposomes in the tumor. In conclusion, the synthesized RF amphiphile leads to efficient liposomal tumor targeting and can be favorably detected by photoacoustic imaging with a perspective of theranostic applications.

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Overcoming the polyethylene glycol dilemma via pathological environment-sensitive change of the surface property of nanoparticles for cellular entry

Cited by 93 publications

References 28 publications

Polyaminoacid–doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy

Polyaminoacid–doxorubicin prodrug micelles as highly selective therapeutics for targeted cancer therapy

Recent progress in development of siRNA delivery vehicles for cancer therapy

Photoacoustic imaging of tumor targeting with riboflavin-functionalized theranostic nanocarriers

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