Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review

Kanamala, Manju; Wilson, William R.; Yang, Mimi; Palmer, Brian D.; Wu, Zimei

doi:10.1016/j.biomaterials.2016.01.061

Cited by 793 publications

(478 citation statements)

References 191 publications

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“…Furthermore, DDLS revealed an increase in hydrodynamic size of approximately 20 nm (Figure 3 B) and a sudden decrease in scattering intensity after an initial steady increase, which could be explained by NP sedimentation resulting from aggregation or increase in shell density (Supporting Information, Figure S7). In our case, the surface grafted polymer is attached to the NPs through electrostatic interaction enabling conformational changes of the polymer in solution22, 23, 24 and possibly acts to stabilize some of the early stages of aggregation, while the larger aggregates are not clearly detectable with DDLS because of the above‐mentioned sedimentation. …”

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confidence: 95%

Assessing the Stability of Fluorescently Encoded Nanoparticles in Lysosomes by Using Complementary Methods

et al. 2017

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Nanoparticles (NPs) are promising tools in biomedical research. In vitro testing is still the first method for initial evaluation; however, NP colloidal behavior and integrity, in particular inside cells (that is, in lysosomes), are largely unknown and difficult to evaluate because of the complexity of the environment. Furthermore, while the majority of NPs are usually labeled with fluorescent dyes for tracking purposes, the effect of the lysosomal environment on the fluorophore properties, as well as the ensuing effects on data interpretation, is often only sparsely addressed. In this work, we have employed several complementary analytical methods to better understand the fate of fluorescently encoded NPs and identify potential pitfalls that may arise from focusing primary analysis on a single attribute, for example, fluorophore detection. Our study shows that in a lysosomal environment NPs can undergo significant changes resulting in dye quenching and distorted fluorescence signals.

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confidence: 95%

Assessing the Stability of Fluorescently Encoded Nanoparticles in Lysosomes by Using Complementary Methods

et al. 2017

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“…CA IX plays critical roles in tumor cells, including cell survival and proliferation, stem cell phenotype maintenance [15], epithelial-mesenchymal transition (EMT) in carcinoma cells [16], invasion, metastasis [17], and resistance to radiation therapy and chemotherapy [18][19][20][21]. Importantly, the accumulation of acidic by-products such as lactic acid, produced by highly metabolic cancer cells involved in glycolytic metabolism, leads to the presence of an increasingly acidified intracellular pH and basic extracellular pH [6,22,23]. Several studies have established that depletion of CA IX gene expression and inhibition of its catalytic activity in the context of hypoxia dysregulate pH homeostasis and affect the viability of several types of cancer cells in vitro [21,24].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of carbonic anhydrase IX in glioblastoma multiforme

Amiri

Moquin

et al. 2016

European Journal of Pharmaceutics and Biopharmaceutics

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a b s t r a c tCarbonic anhydrase IX (CA IX) is a transmembrane enzyme upregulated in several types of tumors including glioblastoma multiforme (GBM). GBM is among the most aggressive tumors among gliomas. Temozolomide (TMZ) therapy combined with surgical or radiation approaches is the standard treatment but not effective in long term. In this study we tested the treatment with acetazolamide (ATZ), an inhibitor of CA IX, alone or combined with TMZ. The experiments were performed in 2D and 3D cultures (spheroids) using glioblastoma U251N and human brain tumor stem cells (BTSCs). Several proteins implicated in tumor cell death were also investigated. The key results from these studies suggest the following: (1) Cell death of human glioblastoma spheroids and BTSC is significantly increased with combined treatment after 7 days, and (2) the effectiveness of ATZ is significantly enhanced against BTSC and U251N when incorporated into nano-carriers. Collectively, these results point toward the usefulness of nano-delivery of CA IX inhibitors and their combination with chemotherapeutics for glioblastoma treatment.

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“…pH-Triggered Release: Acid-labile chemical bonds that are stable in the bloodstream (pH 7.4) but upon endocytic internalization are cleaved in the slightly acidic late endosomal (pH 5-6) and lysosomal (pH 4-5) environments, have been used to promote endolysosomal release. [30][31][32] Among the different pH sensitive linkers, which are available, such as acetal/ketal, [28][29][30][31][32][33][34][35][36][37][38][39][40][41] ortho ester, [30][31][32][42][43][44] imine, [30][31][32]36,[45][46][47][48] oxime, [28,31,36,[49][50][51] and maleic acid amide derivatives, [29,30,32,41,[52][53][54] the hydrazone linker [28][29][30][31]<...>…”

Section: Endolysosomal Releasementioning

confidence: 99%

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

Battistella

Klok

2017

Macromolecular Bioscience

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Polymer nanomedicines are very attractive to improve the delivery of chemotherapeutics. Polymer conjugates and other polymer‐based nanocarriers allow to increase plasma half‐life and drug bioavailability and can also be guided toward tumors using passive and active targeting strategies. Since many chemotherapeutics act on targets that are located in well‐defined subcellular compartments, other important factors that contribute to an efficient therapy include cellular internalization and subsequent intracellular trafficking of the polymer nanomedicines and/or its payload to the appropriate organelle in the cytoplasm. This article provides an overview of the different approaches that have been developed to control intracellular delivery of polymer nanomedicines and discusses the different techniques that can be used to monitor these processes.

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Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review

Cited by 793 publications

References 191 publications

Assessing the Stability of Fluorescently Encoded Nanoparticles in Lysosomes by Using Complementary Methods

Assessing the Stability of Fluorescently Encoded Nanoparticles in Lysosomes by Using Complementary Methods

Inhibition of carbonic anhydrase IX in glioblastoma multiforme

Controlling and Monitoring Intracellular Delivery of Anticancer Polymer Nanomedicines

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