The acidic tumor microenvironment: a target for smart cancer nano-theranostics

Feng, Liangzhu; Dong, Ziliang; Tao, Danlei; Zhang, Yicheng; Liu, Zhuang

doi:10.1093/nsr/nwx062

Cited by 280 publications

(183 citation statements)

References 132 publications

Supporting

Mentioning

181

Contrasting

Order By: Relevance

“…The in vitro release profiles of CPT from the carriers were measured using dialysis membranes as discussed in the experimental section. The loaded drug is released from the carriers well over a period of 45 h, both under the pH conditions of 7.4 and 6.0 at 35 C. The two pH values are chosen as the physiological pH is 7.4 and in the tumour microenvironment the pH is decreased due to acidic metabolites caused by anaerobic glycolysis in hypoxia [37]. The cumulative release of CPT is 65% at pH 7.4 and 38% at pH 6.0 in the case of CPT@DNPs, whereas 73% and 47% at pH 7.4 and 6.0, respectively, in the case of CPT@FDNPs.…”

Section: Drug Loading and Drug Releasementioning

confidence: 99%

Folate-molecular encapsulator-tethered biocompatible polymer grafted with magnetic nanoparticles for augmented drug delivery

Ramasamy

David

Enoch

2018

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

Magnetic ferrite nanoparticles (MNPs) coated with biocompatible polymers capable of drug loading and release are fascinating nanostructures for delivering anti-cancer drugs. Herein, we report the synthesis and characterization of a novel β-cyclodextrin-folate-tethered dextran polymer. Nickel-zinc ferrite nanoparticles are prepared and coated with the polymer to form a biocompatible hybrid magnetic nanocarrier. To establish the significance of folate unit of the polymer in anticancer activity, a similar derivatized polymer, i.e. β-cyclodextrin-dextran conjugate without folate tether is used for comparison. The size of the hybrid MNPs is ∼20 nm, which is a size suitable for cancer drug targeting. The polymer-coated magnetic nanocarriers are soft ferromagnets as suggested by their narrow magnetic hysteresis loops. The anticancer drug camptothecin (CPT) is loaded on the magnetic nanocarriers. The drug loading efficiency is observed to be above 92%. The nanocarriers show sustained in vitro drug release for above 45 h. The in vitro cytotoxicity studies reveal that the loaded CPT retains its potency in the nanocarrier and the folate-tethered nanocarrier shows better anticancer activity than the one which does not carry a folate unit. The magnetic nanocarrier is suitable for magnetic field-guided drug transport, enhanced drug loading and release and folate receptor-mediated endocytotic uptake of drugs by cancer cells.

show abstract

Section: Drug Loading and Drug Releasementioning

confidence: 99%

Folate-molecular encapsulator-tethered biocompatible polymer grafted with magnetic nanoparticles for augmented drug delivery

Ramasamy

David

Enoch

2018

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

show abstract

“…A decrease in pH accelerates the drug release from 54.5% at pH 7.4 to 69.4% at pH 6.0. The two mentioned pH's are chosen for the experiments since 7.4 is the normal physiological and the pH is decreased in the tumour microenvironment due to acidic metabolites caused by anaerobic glycolysis in hypoxia (Feng et al 2018). The larger size of nanoparticles (> 100 nm) results in a slower release of loaded drugs (Zhu et al 2009).…”

Section: Drug Loading and Releasementioning

confidence: 99%

Cyclodextrin–PEG conjugate-wrapped magnetic ferrite nanoparticles for enhanced drug loading and release

et al. 2018

View full text Add to dashboard Cite

Magnetic nanoparticles are envisaged to overcome the impediments in the methods of targeted drug delivery and hence cure cancer effectively. We report herein, manganese ferrite nanoparticles, coated with β-cyclodextrin-modified polyethylene glycol as a carrier for the drug, camptothecin. The particles are of the size of ~ 100 nm and they show superparamagnetic behaviour. The saturation magnetization does not get diminished on polymer coverage of the nanoparticles. The β-cyclodextrin-polyethylene glycol conjugates are characterized using NMR and mass spectrometric techniques. By coating the magnetic nanoparticles with the cyclodextrin-tethered polymer, the drug-loading capacity is enhanced and the observed release of the drug is slow and sustained. The cell viability of HEK293 and HCT15 cells is evaluated and the cytotoxicity is enhanced when the drug is loaded in the polymer-coated magnetic nanoparticles. The noncovalent-binding based and enhanced drug loading on the nanoparticles and the sustained release make the nanocarrier a promising agent for carrying the payload to the target.

show abstract

“…However, such nano‐PSs with relatively large sizes would primarily accumulate around the leaky blood vessels and may only cause partial damages to tumor as a result of their limited intratumor penetration ability under the high tumor interstitial pressure. Therefore, it would be of great significance to develop size shrinkable nano‐PSs in response to tumor localized stimuli to confer efficient tumor accumulation and thereby enhanced intratumor diffusion for improved cancer PDT …”

Section: Introductionmentioning

confidence: 99%

Tumor‐pH‐Responsive Dissociable Albumin–Tamoxifen Nanocomplexes Enabling Efficient Tumor Penetration and Hypoxia Relief for Enhanced Cancer Photodynamic Therapy

Yang

Chen

et al. 2018

Small

Self Cite

104

View full text Add to dashboard Cite

Despite the promises of applying nano‐photosensitizers (nano‐PSs) for photodynamic therapy (PDT) against cancer, severe tumor hypoxia and limited tumor penetration of nano‐PSs would lead to nonoptimized therapeutic outcomes of PDT. Therefore, herein a biocompatible nano‐PS is prepared by using tamoxifen (TAM), an anti‐estrogen compound, to induce self‐assembly of chlorin e6 (Ce6) modified human serum albumin (HSA). The formed HSA–Ce6/TAM nanocomplexes, which are stable under neutral pH with a diameter of ≈130 nm, would be dissociated into individual HSA–Ce6 and TAM molecules under the acidic tumor microenvironment, owing to the pH responsive transition of TAM from hydrophobic to hydrophilic. Upon systemic administration, such HSA–Ce6/TAM nanoparticles exhibit prolonged blood circulation and high accumulation in the tumor, where it would undergo rapid pH responsive dissociation to enable obviously enhanced intratumoral penetration of HSA–Ce6. Furthermore, utilizing the ability of TAM in reducing the oxygen consumption of cancer cells, it is found that HSA–Ce6/TAM after systemic administration could efficiently attenuate the tumor hypoxia status. Those effects acting together lead to remarkably enhanced PDT treatment. This work presents a rather simple approach to fabricate smart nano‐PSs with multiple functions integrated into a single system via self‐assembly of all‐biocompatible components, promising for the next generation cancer PDT.

show abstract

The acidic tumor microenvironment: a target for smart cancer nano-theranostics

Cited by 280 publications

References 132 publications

Folate-molecular encapsulator-tethered biocompatible polymer grafted with magnetic nanoparticles for augmented drug delivery

Folate-molecular encapsulator-tethered biocompatible polymer grafted with magnetic nanoparticles for augmented drug delivery

Cyclodextrin–PEG conjugate-wrapped magnetic ferrite nanoparticles for enhanced drug loading and release

Tumor‐pH‐Responsive Dissociable Albumin–Tamoxifen Nanocomplexes Enabling Efficient Tumor Penetration and Hypoxia Relief for Enhanced Cancer Photodynamic Therapy

Contact Info

Product

Resources

About