Measurement of the extracellular pH of solid tumours in mice by magnetic resonance spectroscopy: a comparison of exogenous19F and31P probes

Ojugo, A. S. E.; McSheehy, Paul M.J.; McIntyre, Dominick J.O.; McCoy, Cheryl L.; Stubbs, Marion; Leach, Martin O.; Judson, Ian; Griffiths, John R.

doi:10.1002/(sici)1099-1492(199912)12:8<495::aid-nbm594>3.0.co;2-k

Cited by 215 publications

(152 citation statements)

References 23 publications

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“…The cell viability expressed in this study is relative to those at each pH in the absence of DOX and micelles and the direct pH effect on the cell viability was not monitored with the MCF-7 cell line. The change in pH from 7.4 to 6.0 may influence cell surface charges and cellular physiology and viability, noting that the low pH is a favorable environment for tumor cells but has detrimental effect on normal cells [26][27][28][29].…”

Section: Ph-dependent Cell Cytotoxicitymentioning

confidence: 99%

“…The extracellular pH (pH e ) in most tumors is more acidic (pH 6.5-7.2) than in normal tissues [27][28][29]. In all measurements (involving either invasive or noninvasive methods) of the pH e of human and animal solid tumors, more than 80% of all measured values consistently fall below a pH of 7.2 [27][28][29]. The development of pH-sensitive drug-carriers therefore maybe a unique strategy and confer advantages over using external stimuli, such as hyperthermia [5] and ultrasound [6] which require exact location of tumors for triggered release [30].…”

Section: Introductionmentioning

confidence: 99%

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Tumor pH-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-histidine)

Lee

Kim

et al. 2007

Journal of Controlled Release

419

267

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Polymeric micelles were constructed from poly(L-lactic acid) (PLA; M n 3K)-b-poly(ethylene glycol) (PEG; M n 2K)-b-poly(L-histidine) (polyHis; M n 5K) as a tumor pH-specific anticancer drug carrier. Micelles (particle diameter: ~ 80 nm; critical micelle concentration (CMC): 2 µg/ml) formed by dialysis of the polymer solution in dimethylsulfoxide (DMSO) against pH 8.0 aqueous solution, are assumed to have a flower-like assembly of PLA and polyHis blocks in the core and PEG block as the shell. The pH-sensitivity of the micelles originates from the deformation of the micellar core due to the ionization of polyHis at a slightly acidic pH. However, the co-presence of pH-insensitive lipophilic PLA block in the core prevented disintegration of the micelles and caused swelling/ aggregation. A fluorescence probe study showed that the polarity of pyrene retained in the micelles increased as pH was decreased from 7.4 to 6.6, indicating a change to a more hydrophilic environment in the micelles. Considering that the size increased up to 580 nm at pH 6.6 from 80 nm at pH 7.4 and that the transmittance of micellar solution increased with decreasing pH, the micelles were not dissociated but rather swollen/aggregated. Interestingly, the subsequent decline of pyrene polarity below pH 6.6 suggested re-self-assembly of the block copolymers, most likely forming a PLA block core while polyHis block relocation to the surface. Consequently, these pH-dependent physical changes of the PLA-b-PEG-b-polyHis micelles provide a mechanism for triggered drug release from the micelles triggered by the small change in pH (pH 7.2-6.5).

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Section: Ph-dependent Cell Cytotoxicitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Tumor pH-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-histidine)

Lee

Kim

et al. 2007

Journal of Controlled Release

419

267

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“…The pH values measured in most solid tumors range from 5.7 to 7.8, with a mean of 7.0 (Ojugo et al, 1999). The essential part of a pH-sensitive drug delivery system is a pH-triggering group (an ionizable weak acidic or basic moiety) that is attached to the backbone.…”

Section: Ph-sensitive Polymersmentioning

confidence: 99%

Classification of stimuli–responsive polymers as anticancer drug delivery systems

et al. 2014

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Although several anticancer drugs have been introduced as chemotherapeutic agents, the effective treatment of cancer remains a challenge. Major limitations in the application of anticancer drugs include their nonspecificity, wide biodistribution, short half-life, low concentration in tumor tissue and systemic toxicity. Drug delivery to the tumor site has become feasible in recent years, and recent advances in the development of new drug delivery systems for controlled drug release in tumor tissues with reduced side effects show great promise. In this field, the use of biodegradable polymers as drug carriers has attracted the most attention. However, drug release is still difficult to control even when a polymeric drug carrier is used. The design of pharmaceutical polymers that respond to external stimuli (known as stimuli-responsive polymers) such as temperature, pH, electric or magnetic field, enzymes, ultrasound waves, etc. appears to be a successful approach. In these systems, drug release is triggered by different stimuli. The purpose of this review is to summarize different types of polymeric drug carriers and stimuli, in addition to the combination use of stimuli in order to achieve a better controlled drug release, and it discusses their potential strengths and applications. A survey of the recent literature on various stimuli-responsive drug delivery systems is also provided and perspectives on possible future developments in controlled drug release at tumor site have been discussed.

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“…Here, it is exploited that the extracellular pH of tumor tissues is more acidic than the pH of the surrounding healthy tissues. 141 Moreover, the pH of intracellular lysosomes or endosmomes is shifted to more acidic values than the cytosolic pH. 142 Based on these considerations, Das et al…”

Section: Temperature-sensitive Microgelsmentioning

confidence: 99%

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

Klinger

2013

Springer Theses

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This thesis focuses on the design, synthesis and characterization of novel photo-sensitive microgels and nanoparticles as potential materials for the loading and light-triggered release/accessibility of functional compounds. In order to realize this concept, different approaches to irradiation-dependent response mechanisms have been investigated.Novel light-cleavable divinyl functionalized monomeric crosslinkers based on o-nitrobenzyl derivatives were synthesized and used for the preparation of either PMMA or hydroxyl functionalized PHEMA microgels swellable and degradable in organic solvents. By the introduction of anionic MAA moieties into the PHEMA microgels, this concept was successfully transferred to double stimuli-responsive p(HEMA-co-MAA) hydrogel nanoparticles exhibiting a pH-dependent swelling and light-induced degradation behavior in aqueous media. This sensitivity to two orthogonal triggers is proposed to combine a pHinduced post-formation loading mechanism with a pH-and light-triggered release. In addition, a new class of enzyme-and light-sensitive PAAm microgels based on (meth-)acrylate functionalized dextrans as photo-and enzymatically degradable macromolecular crosslinkers was developed by introducing a photo-labile linker between the enzymatically degradable dextran chain and the polymerizable vinyl moieties. Here, the water solubility of the crosslinkers is assumed to enable an in situ loading approach of hydrophilic compounds.A different approach to the loading of microgels is based on photo-labile covalent microgel-drug conjugates. The first step to the realization of this concept was achieved by the development of a novel functional monomer consisting of a doxorubicin molecule covalently attached to a radically polymerizable methacrylate group via a photo-cleavable linker.Moreover, in order to enable the release of hydrophobic substances in aqueous media, hydrophobic nanoparticles consisting of a photo-resist polymer were designed to be degradable upon irradiation in water. Light-triggered conversion of the initial hydrophobic polymer into hydrophilic PMAA induced in situ particle dissolution and release of nile red.Since the introduction of a stimuli-responsive shell around a microgel is assumed to prevent leakage of embedded compounds, studies on non-stimuli-responsive shell formation around preformed microgel seed particles and the formation of microgel cores in polymeric shells were conducted to investigate potential synthetic pathways to this approach.In a last attempt, the surface of PHEMA and p(HEMA-co-MAA) microgels was functionalized with cinnamoyl groups in order to trigger the (reversible) particles interaction with each other by light-induced [2+2] cycloaddition reactions.

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Measurement of the extracellular pH of solid tumours in mice by magnetic resonance spectroscopy: a comparison of exogenous19F and31P probes

Cited by 215 publications

References 23 publications

Tumor pH-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-histidine)

Tumor pH-responsive flower-like micelles of poly(l-lactic acid)-b-poly(ethylene glycol)-b-poly(l-histidine)

Classification of stimuli–responsive polymers as anticancer drug delivery systems

Light-Sensitive Polymeric Nanoparticles Based on Photo-Cleavable Chromophores

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