Engineering Lipid Vesicles of Enhanced Intratumoral Transport Capabilities: Correlating Liposome Characteristics with Penetration into Human Prostate Tumor Spheroids

Kostarelos, Kostas; Emfietzoglou, Dimitris; Papakostas, Alexandros; Yang, Wei; Ballangrud, Åse M.; Antonarakis, Emmanuel S.

doi:10.1081/lpr-200064953

Cited by 13 publications

(15 citation statements)

References 20 publications

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“…4B). High IFP and low diffusion and convection will influence the penetration depths of liposomes, as reported in multicellular tumor spheroids (43, 44) and in experimental solid tumors (45) and thus the relative distribution of the tracers is likely to indicate the distribution of large pores. PET is an effective method to map the relative concentration of tracers over time and space, where maximum-intensity-projection images and contour maps were each useful in visualizing variations in accumulation.…”

Section: Discussionmentioning

confidence: 94%

Longitudinal Investigation of Permeability and Distribution of Macromolecules in Mouse Malignant Transformation Using PET

Rygh

Qin

Seo

et al. 2011

Clinical Cancer Research

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Purpose: We apply positron emission tomography (PET) to elucidate changes in nanocarrier extravasation during the transition from premalignant to malignant cancer, providing insight into the use of imaging to characterize early cancerous lesions and the utility of nanoparticles in early disease.Experimental Design: Albumin and liposomes were labeled with 64 Cu (half-life 12.7 hours), and longitudinal PET and CT imaging studies were conducted in a mouse model of ductal carcinoma in situ. A pharmacokinetic model was applied to estimate the tumor vascular volume and permeability.Results: From early time points characterized by disseminated hyperproliferation, the enhanced vascular permeability facilitated lesion detection. During disease progression, the vascular volume fraction increased 1.6-fold and the apparent vascular permeability to albumin and liposomes increased $2.5-fold to 6.6 Â 10 À8 and 1.3 Â 10 À8 cm/s, respectively, with the accumulation of albumin increasing earlier in the disease process. In the malignant tumor, both tracers reached similar mean intratumoral concentrations of $6% ID/cc but the distribution of liposomes was more heterogeneous, ranging from 1% to 18% ID/cc compared with 1% to 9% ID/cc for albumin. The tumor-to-muscle ratio was 17.9 AE 8.1 and 7.1 AE 0.5 for liposomes and albumin, respectively, indicating a more specific delivery of liposomes than with albumin. Conclusions: PET imaging of radiolabeled particles, validated by confocal imaging and histology, detected the transition from premalignant to malignant lesions and effectively quantified the associated changes in vascular permeability.

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Section: Discussionmentioning

confidence: 94%

Longitudinal Investigation of Permeability and Distribution of Macromolecules in Mouse Malignant Transformation Using PET

Rygh

Qin

Seo

et al. 2011

Clinical Cancer Research

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“…Curcumin has been shown to be cancer chemopreventive in several different animal tumor bioassay systems including colon (2,3), duodenal (4), stomach (5), prostate (6) and breast (7) carcinogenesis both in vitro and in vivo. Absence of dose limiting toxicity, when curcumin is administered up to 8 g/day in human clinical trials, reveals the possibility of curcumin in the prevention and treatment of cancer (8,9).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of a nanotechnology-based carrier for delivery of curcumin in prostate cancer cells

Thangapazham

Puri²,

Tele³

et al. 2008

Int J Oncol

112

111

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Abstract.We have initiated studies to enhance targeted delivery of an anticancer agent, curcumin, for prostate cancer treatment by incorporating this agent into the liposomes (nanodelivery vehicles primarily composed of phospholipids) coated with prostate membrane specific antigen specific antibodies. We prepared curcumin-loaded liposomes of various lipid compositions by sonication at an average size of 100-150 nm. Un-entrapped curcumin was removed by size exclusion chromatography. Data show that curcumin preferentially partitioned into liposomes prepared from dimyristoyl phosphatidyl choline (DMPC) and cholesterol among the various compositions tested. The anti-proliferative activity of liposomal curcumin was studied using two human prostate cancer cell lines (LNCaP and C4-2B) by a tetrazolium dyebased (MTT) assay. Treatment of cells with liposomal curcumin (5-10 μM) for 24-48 h at 37˚C resulted in at least 70-80% inhibition of cellular proliferation without affecting their viability. On the other hand, free curcumin exhibited similar inhibition only at 10-fold higher doses (>50 μM). We also observed that LNCaP cells were relatively more sensitive to liposomal curcumin mediated block of cellular proliferation than C4-2B cells. We are currently developing liposome formulations with targeting ability to further improve the efficacy of curcumin in vivo.

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“…In‐vitro multicellular tumour spheroid (MCTS) models mimic true solid tumours, and therefore, intact spheroids may offer similar resistance to the penetration of molecules. The blood–brain barrier spheroids also used for screening and identification of CPPs .…”

Section: Introductionmentioning

confidence: 99%

“…[23][24][25] The mechanisms through which the cell penetrating peptides translocate the cell membrane and deliver drug molecules into the nucleus are believed to be endocytosis and direct translocation. [26] In-vitro multicellular tumour spheroid (MCTS) models mimic true solid tumours, [27][28][29][30] and therefore, intact spheroids may offer similar resistance to the penetration of molecules. The blood-brain barrier spheroids also used for screening and identification of CPPs.…”

Section: Introductionmentioning

confidence: 99%

Transport of trans-activator of transcription (TAT) peptide in tumour tissue model: evaluation of factors affecting the transport of TAT evidenced by flow cytometry

Rаhmаn

Khan

2020

Journal of Pharmacy and Pharmacology

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Objectives Trans‐activator of transcription (TAT), a cell penetrating peptide, has been explored to overcome resistance to penetration and transport inside the cell, therefore, suggested to be used as drug delivery vector into drug‐resistant tumours. The generosity of this study was to evaluate modifiable factors (concentration, temperature, incubation time and spheroid age) on the penetration of TAT. Methods Multicellular tumour spheroids (MCTS) used as tumour tissue models to mimic some characteristics with in‐vivo tumors. Cell monolayer and 3‐, 5‐, 7‐day‐old MCTS were incubated with TAT and effects of modifiable factors were determined quantitatively through flow cytometry, based on TAT‐positive cell count (%) and mean fluorescence intensity. Key findings Enhancing TAT concentration (1, 5 and 25 µm), transport significantly increased (ANOVA, P < 0.0001) in cell monolayer and spheroids. However, rising temperature from 7 to 37°C (t, P > 0.05) and increasing incubation time; 20 min, 1 h and 3 h; (ANOVA, P > 0.05) were statistically non‐significant. Moreover, TAT penetration declines as spheroids get older (ANOVA, P < 0.01). Conclusion While exploiting MCTS as tumour tissue model, older spheroids could be preferred to target penetration‐resistant cells and mimic the in‐vivo microenvironment.

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Engineering Lipid Vesicles of Enhanced Intratumoral Transport Capabilities: Correlating Liposome Characteristics with Penetration into Human Prostate Tumor Spheroids

Cited by 13 publications

References 20 publications

Longitudinal Investigation of Permeability and Distribution of Macromolecules in Mouse Malignant Transformation Using PET

Longitudinal Investigation of Permeability and Distribution of Macromolecules in Mouse Malignant Transformation Using PET

Evaluation of a nanotechnology-based carrier for delivery of curcumin in prostate cancer cells

Transport of trans-activator of transcription (TAT) peptide in tumour tissue model: evaluation of factors affecting the transport of TAT evidenced by flow cytometry

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