In vivo and in vitro anti-cancer activities and enhanced cellular uptakes of EGF fragment decorated doxorubicin nano-aggregates

Park, Shinyoung; Yoo, Hyuk Sang

doi:10.1016/j.ijpharm.2009.08.039

Cited by 19 publications

(5 citation statements)

References 27 publications

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“…Various types of targeted nanoparticles (including liposomes) have been used successfully to deliver whole body imaging sensors and/or therapeutic agents into tumors in vivo 55 due to Enhanced Permeability and Retention effect 45, which is a combination of leaky tumor endothelium with wide fenestrations, in combination with a lack of effective lymphatic drainage. The efficiency of delivering the imaging sensors can be further improved by using antibody- or peptide-based 41 approaches to target the liposomes to tumor cells that have an overexpression of EGFR (19, 36).…”

Section: Introductionmentioning

confidence: 99%

Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor

et al. 2017

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Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity. For sensing EGFR activity in cells, we used a genetically encoded CrkII-based biosensor which undergoes conformational changes upon tyrosine-221 phosphorylation by EGFR. We transfected this biosensor into EGFR-positive tumour cells using targeted lipopolyplexes bearing EGFR-binding peptides at their surfaces. In a murine model of basal-like breast cancer, we demonstrated a significant degree of intratumoral heterogeneity in EGFR activity, as well as the pharmacodynamic effect of a radionuclide-labeled EGFR inhibitor in situ. Furthermore, a significant correlation between high EGFR activity in tumour cells and macrophage-tumour cell proximity was found to in part account for the intratumoral heterogeneity in EGFR activity observed. The same effect of macrophage infiltrate on EGFR activation was also seen in a colorectal cancer xenograft. In contrast, a non-small cell lung cancer xenograft expressing a constitutively active EGFR conformational mutant exhibited macrophage proximity-independent EGFR activity. Our study validates the use of this methodology to monitor therapeutic response in terms of EGFR activity. In addition, we found iNOS gene induction in macrophages that are cultured in tumour cell-conditioned media as well as an iNOS activity-dependent increase in EGFR activity in tumour cells. These findings point towards an immune microenvironment-mediated regulation that gives rise to the observed intratumoral heterogeneity of EGFR signalling activity in tumour cells in vivo.

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Section: Introductionmentioning

confidence: 99%

Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor

et al. 2017

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“…EGF-based targeted delivery has previously been used in cancer chemotherapeutics. The EGF or EGFR antibody can be used as the tumour-targeting ligand for TDDS with an active targeting function to bypass EGFR-mediated endocytosis [19,20,44,45]. Our results clearly indicate that EGF could be an excellent targeting moiety with high-efficiency active targeting and low cell toxicity.…”

Section: (B))mentioning

confidence: 70%

EGF-functionalized single-walled carbon nanotubes for targeting delivery of etoposide

et al. 2012

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To enhance the therapeutic potential of etoposide (ETO), we devised a targeted drug delivery system (TDDS) of epidermal growth factor-chitosan-carboxyl single-walled carbon nanotubes-ETO (EGF/CHI/SWNT-COOHs/ETO) using modified SWNTs (m-SWNTs) as the carrier, EGF-functionalized SWNTs (f-SWNTs) as the targeted moiety and ETO as the drug. After SWNT-COOHs were conjugated with CHI (CHI/SWNT-COOHs/ETO), they displayed high solubility and stable dispersion in aqueous solution. The drug loading capacity was approximately 25-27%. The m-SWNTs and f-SWNTs had only slight cytotoxicity. ETO was released from EGF/CHI/SWNT-COOHs/ETO at low pH and taken up by tumour cells via adenosine triphosphate (ATP)-dependent endocytosis. The cell death induced by EGF/CHI/SWNT-COOHs/ETO was as much as 2.7 times that due to ETO alone. In summary, these results demonstrated that our TDDS had a greater anticancer effect than free ETO in vitro.

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“…Recently, Park and Yoo conjugated an EGF-fragment (11 amino acid peptide) and doxorubicin (DOX) to a bi-functional PEG-polymer. After mixing the conjugate, free DOX and triethylamine “nano-aggregates” spontaneously formed and showed a higher anti-tumor effect in animals bearing human lung-carcinoma xenografts (Park and Yoo, 2009). In a paper by Diagaradjane et al EGF targeted fluorescent quantum dots were successfully employed for the noninvasive optical imaging of EGFR expression in human colorectal cancer xenografts in mice (Diagaradjane et al, 2008).…”

Section: Vascular Targeting Moietiesmentioning

confidence: 99%

An Integrated Approach for the Rational Design of Nanovectors for Biomedical Imaging and Therapy

Godin

Driessen

Proneth

et al. 2010

Advances in Genetics

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The use of nanoparticles for the early detection, cure and imaging of diseases has been proved already to have enormous potentials in different biomedical fields, as oncology and cardiology. A broad spectrum of nanoparticles are currently under development exhibiting differences in (i) size, ranging from few tens of nanometers to few microns; (ii) shape, from the classical spherical beads to discoidal, hemispherical, cylindrical and conical; (iii) surface functionalization, with a wide range of electrostatic charges and bio-molecule conjugations. Clearly, the library of nanoparticles generated by combining all possible sizes, shapes and surface physico-chemical properties is enormous. With such a complex scenario, an integrated approach is here proposed and described for the rational design of nanoparticle systems (nanovectors) for the intravascular delivery of therapeutic and imaging contrast agents. The proposed integrated approach combines multi-scale/multi-physics mathematical models with in-vitro assays and in-vivo intravital microscopy experiments and aims at identifying the optimal combination of size, shape and surface properties that maximize the nanovectors localization within the diseased microvasculature.

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In vivo and in vitro anti-cancer activities and enhanced cellular uptakes of EGF fragment decorated doxorubicin nano-aggregates

Cited by 19 publications

References 27 publications

Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor

Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor

EGF-functionalized single-walled carbon nanotubes for targeting delivery of etoposide

An Integrated Approach for the Rational Design of Nanovectors for Biomedical Imaging and Therapy

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