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Article: Pt(II)-PLGA Hybrid in a pH-Responsive Nanoparticle System Targeting Ovarian Cancer.

Wlodarczyk, Marek T / Dragulska, Sylwia A / Chen, Ying / Poursharifi, Mina / Acosta Santiago, Maxier / Martignetti, John A / Mieszawska, Aneta J

Pharmaceutics

2023 Volume 15, Issue 2

Abstract: Platinum-based agents are the main treatment option in ovarian cancer (OC). Herein, we report a poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) encapsulating platinum (II), which is targeted to a cell-spanning protein overexpressed in above 90% of ...

Abstract	Platinum-based agents are the main treatment option in ovarian cancer (OC). Herein, we report a poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) encapsulating platinum (II), which is targeted to a cell-spanning protein overexpressed in above 90% of late-stage OC, mucin 1 (MUC1). The NP is coated with phospholipid-DNA aptamers against MUC1 and a pH-sensitive PEG derivative containing an acid-labile hydrazone linkage. The pH-sensitive PEG serves as an off-on switch that provides shielding effects at the physiological pH and is shed at lower pH, thus exposing the MUC1 ligands. The pH-MUC1-Pt NPs are stable in the serum and display pH-dependent PEG cleavage and drug release. Moreover, the NPs effectively internalize in OC cells with higher accumulation at lower pH. The Pt (II) loading into the NP was accomplished via PLGA-Pt (II) coordination chemistry and was found to be 1.62 wt.%. In vitro screening using a panel of OC cell lines revealed that pH-MUC1-Pt NP has a greater effect in reducing cellular viability than carboplatin, a clinically relevant drug analogue. Biodistribution studies have demonstrated NP accumulation at tumor sites with effective Pt (II) delivery. Together, these results demonstrate a potential for pH-MUC1-Pt NP for the enhanced Pt (II) therapy of OC and other solid tumors currently treated with platinum agents.
Language	English
Publishing date	2023-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics15020607
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Engineering and Validation of a Peptide-Stabilized Poly(lactic-

Dragulska, Sylwia A / Poursharifi, Mina / Chen, Ying / Wlodarczyk, Marek T / Acosta Santiago, Maxier / Dottino, Peter / Martignetti, John A / Mieszawska, Aneta J

Bioconjugate chemistry

2022 Volume 33, Issue 12, Page(s) 2348–2360

Abstract: Developing a biocompatible and biodegradable nanoparticle (NP) carrier that integrates drug-loading capability, active targeting, and imaging modality is extremely challenging. Herein, we report an NP with a core of poly(lactic- ...

Abstract	Developing a biocompatible and biodegradable nanoparticle (NP) carrier that integrates drug-loading capability, active targeting, and imaging modality is extremely challenging. Herein, we report an NP with a core of poly(lactic-
MeSH term(s)	Humans ; Mice ; Animals ; Polylactic Acid-Polyglycolic Acid Copolymer ; Polyglycolic Acid ; Lactic Acid ; Endothelial Cells ; Peptides ; Polyethylene Glycols ; Drug Delivery Systems ; Neoplasms ; Nanoparticles
Chemical Substances	Polylactic Acid-Polyglycolic Acid Copolymer (1SIA8062RS) ; Polyglycolic Acid (26009-03-0) ; Lactic Acid (33X04XA5AT) ; Peptides ; Polyethylene Glycols (3WJQ0SDW1A)
Language	English
Publishing date	2022-11-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.2c00418
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Article: A tripeptide-stabilized nanoemulsion of oleic acid

Dragulska, Sylwia A / Wlodarczyk, Marek T / Poursharifi, Mina / Martignetti, John A / Mieszawska, Aneta J

Journal of visualized experiments. 2019 Feb. 27, , no. 144

2019

Abstract: We describe a method to produce a nanoemulsion composed of an oleic acids-Pt(II) core and a lysine-tyrosine-phenylalanine (KYF) coating (KYF-Pt-NE). The KYF-Pt-NE encapsulates Pt(II) at 10 wt. %, has a diameter of 107 ± 27 nm and a negative surface ... ...

Abstract	We describe a method to produce a nanoemulsion composed of an oleic acids-Pt(II) core and a lysine-tyrosine-phenylalanine (KYF) coating (KYF-Pt-NE). The KYF-Pt-NE encapsulates Pt(II) at 10 wt. %, has a diameter of 107 ± 27 nm and a negative surface charge. The KYF-Pt-NE is stable in water and in serum, and is biologically active. The conjugation of a fluorophore to KYF allows the synthesis of a fluorescent nanoemulsion that is suitable for biological imaging. The synthesis of the nanoemulsion is performed in an aqueous environment, and the KYF-Pt-NE forms via self-assembly of a short KYF peptide and an oleic acids-platinum(II) conjugate. The self-assembly process depends on the temperature of the solution, the molar ratio of the substrates, and the flow rate of the substrate addition. Crucial steps include maintaining the optimal stirring rate during the synthesis, permitting sufficient time for self-assembly, and pre-concentrating the nanoemulsion gradually in a centrifugal concentrator.
Keywords	blood serum ; coatings ; fluorescence ; fluorescent dyes ; image analysis ; mixing ; nanoemulsions ; oleic acid ; peptides ; temperature
Language	English
Dates of publication	2019-0227
Size	p. e59034.
Publishing place	Journal of Visualized Experiments
Document type	Article
ISSN	1940-087X
DOI	10.3791/59034
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: A Tripeptide-Stabilized Nanoemulsion of Oleic Acid.

Dragulska, Sylwia A / Wlodarczyk, Marek T / Poursharifi, Mina / Martignetti, John A / Mieszawska, Aneta J

Journal of visualized experiments : JoVE

2019 , Issue 144

Abstract	We describe a method to produce a nanoemulsion composed of an oleic acids-Pt(II) core and a lysine-tyrosine-phenylalanine (KYF) coating (KYF-Pt-NE). The KYF-Pt-NE encapsulates Pt(II) at 10 wt. %, has a diameter of 107 ± 27 nm and a negative surface charge. The KYF-Pt-NE is stable in water and in serum, and is biologically active. The conjugation of a fluorophore to KYF allows the synthesis of a fluorescent nanoemulsion that is suitable for biological imaging. The synthesis of the nanoemulsion is performed in an aqueous environment, and the KYF-Pt-NE forms via self-assembly of a short KYF peptide and an oleic acids-platinum(II) conjugate. The self-assembly process depends on the temperature of the solution, the molar ratio of the substrates, and the flow rate of the substrate addition. Crucial steps include maintaining the optimal stirring rate during the synthesis, permitting sufficient time for self-assembly, and pre-concentrating the nanoemulsion gradually in a centrifugal concentrator.
MeSH term(s)	Emulsions/chemistry ; Lysine/chemistry ; Nanostructures/chemistry ; Oleic Acid/chemistry ; Peptides/chemistry ; Phenylalanine/chemistry ; Platinum/chemistry ; Tyrosine/chemistry
Chemical Substances	Emulsions ; Peptides ; Oleic Acid (2UMI9U37CP) ; Tyrosine (42HK56048U) ; Phenylalanine (47E5O17Y3R) ; Platinum (49DFR088MY) ; Lysine (K3Z4F929H6)
Language	English
Publishing date	2019-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/59034
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Smart biomaterials - regulating cell behavior through signaling molecules.

Mieszawska, Aneta J / Kaplan, David L

BMC biology

2010 Volume 8, Page(s) 59

Abstract: Important advances in the field of tissue engineering are arising from increased interest in novel biomaterial designs with bioactive components that directly influence cell behavior. Following the recent work of Mitchell and co-workers published in BMC ... ...

Abstract	Important advances in the field of tissue engineering are arising from increased interest in novel biomaterial designs with bioactive components that directly influence cell behavior. Following the recent work of Mitchell and co-workers published in BMC Biology, we review how spatial and temporal control of signaling molecules in a matrix material regulates cellular responses for tissue-specific applications.
MeSH term(s)	Biocompatible Materials ; Bone Morphogenetic Protein 2/metabolism ; Cell Proliferation ; Cell Survival/physiology ; Leukemia Inhibitory Factor/metabolism ; Nerve Growth Factor/metabolism ; Nerve Regeneration/physiology ; Neurons/physiology ; Osteogenesis/physiology ; Osteopontin/metabolism ; Signal Transduction/genetics ; Tissue Engineering/methods ; Tissue Engineering/trends
Chemical Substances	Biocompatible Materials ; Bone Morphogenetic Protein 2 ; Leukemia Inhibitory Factor ; Osteopontin (106441-73-0) ; Nerve Growth Factor (9061-61-4)
Language	English
Publishing date	2010-05-19
Publishing country	England
Document type	Comment ; Journal Article ; Review
ISSN	1741-7007
ISSN (online)	1741-7007
DOI	10.1186/1741-7007-8-59
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Article ; Online: Smart biomaterials - regulating cell behavior through signaling molecules

Kaplan David L / Mieszawska Aneta J

BMC Biology, Vol 8, Iss 1, p

2010 Volume 59

Abstract: Abstract Important advances in the field of tissue engineering are arising from increased interest in novel biomaterial designs with bioactive components that directly influence cell behavior. Following the recent work of Mitchell and co-workers ... ...

Abstract	Abstract Important advances in the field of tissue engineering are arising from increased interest in novel biomaterial designs with bioactive components that directly influence cell behavior. Following the recent work of Mitchell and co-workers published in BMC Biology , we review how spatial and temporal control of signaling molecules in a matrix material regulates cellular responses for tissue-specific applications. See research article http://www.biomedcentral.com/1741-7007/8/57
Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2010-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Tripeptide-Stabilized Oil-in-Water Nanoemulsion of an Oleic Acids-Platinum(II) Conjugate as an Anticancer Nanomedicine.

Dragulska, Sylwia A / Chen, Ying / Wlodarczyk, Marek T / Poursharifi, Mina / Dottino, Peter / Ulijn, Rein V / Martignetti, John A / Mieszawska, Aneta J

Bioconjugate chemistry

2018 Volume 29, Issue 8, Page(s) 2514–2519

Abstract: We report a nanoemulsion (NE) which is stabilized by self-assembling tripeptide lysine-tyrosine-phenylalanine (KYF) and encapsulates an oleic acids-platinum conjugate formed using simple Pt (II) coordination chemistry. The KYF-Pt-NE is evaluated both in ... ...

Abstract	We report a nanoemulsion (NE) which is stabilized by self-assembling tripeptide lysine-tyrosine-phenylalanine (KYF) and encapsulates an oleic acids-platinum conjugate formed using simple Pt (II) coordination chemistry. The KYF-Pt-NE is evaluated both in cultured ovarian cancer cells and in an in vivo preclinical cancer model and shows pH dependent Pt (II) release, which is low at physiological pH and enhanced at tumoral pH. The biological activity of KYF-Pt-NE, evaluated in multiple ovarian cancer cell lines, is significantly higher when compared to the analogous Pt (II) complex used in the clinic. Concurrently, the KYF-Pt-NE platform shows good compatibility with the immune system. Preliminary in vivo testing of KYF-Pt-NE with tumor bearing mice indicates efficient Pt (II) delivery to the tumor. Together, these results demonstrate the potential of peptide-stabilized nanoemulsions, specifically KYF-Pt-NE as an effective nanomedicine against cancer.
MeSH term(s)	Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Emulsions ; Female ; Humans ; Mice ; Nanomedicine ; Oils/chemistry ; Oleic Acids/chemistry ; Oligopeptides/chemistry ; Organoplatinum Compounds/chemistry ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/pathology ; Water ; Xenograft Model Antitumor Assays
Chemical Substances	Antineoplastic Agents ; Emulsions ; Oils ; Oleic Acids ; Oligopeptides ; Organoplatinum Compounds ; Water (059QF0KO0R)
Language	English
Publishing date	2018-07-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1024041-x
ISSN	1520-4812 ; 1043-1802
ISSN (online)	1520-4812
ISSN	1043-1802
DOI	10.1021/acs.bioconjchem.8b00409
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Article: Platinum (II) complex-nuclear localization sequence peptide hybrid for overcoming platinum resistance in cancer therapy.

Wlodarczyk, Marek T / Dragulska, Sylwia A / Camacho-Vanegas, Olga / Dottino, Peter R / Jarzęcki, Andrzej A / Martignetti, John A / Mieszawska, Aneta J

ACS biomaterials science & engineering

2018 Volume 4, Issue 2, Page(s) 463–467

Abstract: Platinum therapy represents first line of treatment in many malignancies but its high systemic toxicity limits the therapeutic dosage. Herein, we report the synthesis of carboplatin-like complexes with azide and alkyne functional groups and the formation ...

Abstract	Platinum therapy represents first line of treatment in many malignancies but its high systemic toxicity limits the therapeutic dosage. Herein, we report the synthesis of carboplatin-like complexes with azide and alkyne functional groups and the formation of a platinum (II) - nuclear localization sequence peptide (Pt-NLS) hybrid to improve the import of platinum (II) complexes directly into the cell's nucleus. The Pt-NLS hybrid successfully enters cells and their nuclei, forming Pt-induced nuclear lesions. The in vitro efficacy of Pt-NLS is high, superior to native carboplatin at the same concentration. The methodology used is simple and cost-effective and most importantly can easily be extended to load the Pt (II) onto other supports, opening new possibilities for enhanced delivery of Pt (II) therapy.
Language	English
Publishing date	2018-01-09
Publishing country	United States
Document type	Journal Article
ISSN	2373-9878
ISSN	2373-9878
DOI	10.1021/acsbiomaterials.7b00921
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Multifunctional gold nanoparticles for diagnosis and therapy of disease.

Mieszawska, Aneta J / Mulder, Willem J M / Fayad, Zahi A / Cormode, David P

Molecular pharmaceutics

2013 Volume 10, Issue 3, Page(s) 831–847

Abstract: Gold nanoparticles (AuNPs) have a number of physical properties that make them appealing for medical applications. For example, the attenuation of X-rays by gold nanoparticles has led to their use in computed tomography imaging and as adjuvants for ... ...

Abstract	Gold nanoparticles (AuNPs) have a number of physical properties that make them appealing for medical applications. For example, the attenuation of X-rays by gold nanoparticles has led to their use in computed tomography imaging and as adjuvants for radiotherapy. AuNPs have numerous other applications in imaging, therapy and diagnostic systems. The advanced state of synthetic chemistry of gold nanoparticles offers precise control over physicochemical and optical properties. Furthermore gold cores are inert and are considered to be biocompatible and nontoxic. The surface of gold nanoparticles can easily be modified for a specific application, and ligands for targeting, drugs or biocompatible coatings can be introduced. AuNPs can be incorporated into larger structures such as polymeric nanoparticles or liposomes that deliver large payloads for enhanced diagnostic applications, efficiently encapsulate drugs for concurrent therapy or add additional imaging labels. This array of features has led to the aforementioned applications in biomedical fields, but more recently in approaches where multifunctional gold nanoparticles are used for multiple methods, such as concurrent diagnosis and therapy, so-called theranostics. This review covers basic principles and recent findings in gold nanoparticle applications for imaging, therapy and diagnostics, with a focus on reports of multifunctional AuNPs.
MeSH term(s)	Diagnostic Imaging/methods ; Gold/chemistry ; Humans ; Metal Nanoparticles/therapeutic use
Chemical Substances	Gold (7440-57-5)
Language	English
Publishing date	2013-02-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2138405-8
ISSN	1543-8392 ; 1543-8384
ISSN (online)	1543-8392
ISSN	1543-8384
DOI	10.1021/mp3005885
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Article ; Online: Inorganic nanocrystals as contrast agents in MRI: synthesis, coating and introduction of multifunctionality.

Cormode, David P / Sanchez-Gaytan, Brenda L / Mieszawska, Aneta J / Fayad, Zahi A / Mulder, Willem J M

NMR in biomedicine

2013 Volume 26, Issue 7, Page(s) 766–780

Abstract: Inorganic nanocrystals have myriad applications in medicine, including their use as drug or gene delivery complexes, therapeutic hyperthermia agents, in diagnostic systems and as contrast agents in a wide range of medical imaging techniques. In MRI, ... ...

Abstract	Inorganic nanocrystals have myriad applications in medicine, including their use as drug or gene delivery complexes, therapeutic hyperthermia agents, in diagnostic systems and as contrast agents in a wide range of medical imaging techniques. In MRI, nanocrystals can produce contrast themselves, with iron oxides having been the most extensively explored, or can be given a coating that generates MR contrast, for example gold nanoparticles coated with gadolinium chelates. These MR-active nanocrystals can be used for imaging of the vasculature, liver and other organs, as well as molecular imaging, cell tracking and theranostics. As a result of these exciting applications, the synthesis and rendering of these nanocrystals as water soluble and biocompatible are therefore highly desirable. We discuss aqueous phase and organic phase methods for the synthesis of inorganic nanocrystals, such as gold, iron oxides and quantum dots. The pros and cons of the various methods are highlighted. We explore various methods for making nanocrystals biocompatible, i.e. direct synthesis of nanocrystals coated with biocompatible coatings, ligand substitution, amphiphile coating and embedding in carrier matrices that can be made biocompatible. Various examples are highlighted and their applications explained. These examples signify that the synthesis of biocompatible nanocrystals with controlled properties has been achieved by numerous research groups and can be applied to a wide range of applications. Therefore, we expect to see reports of preclinical applications of ever more complex MRI-active nanoparticles and their wider exploitation, as well as in novel clinical settings.
MeSH term(s)	Animals ; Biocompatible Materials/chemical synthesis ; Contrast Media/chemical synthesis ; Contrast Media/chemistry ; Humans ; Hydrophobic and Hydrophilic Interactions ; Inorganic Chemicals/chemical synthesis ; Inorganic Chemicals/chemistry ; Magnetic Resonance Imaging ; Nanoparticles/chemistry ; Nanoparticles/ultrastructure
Chemical Substances	Biocompatible Materials ; Contrast Media ; Inorganic Chemicals
Language	English
Publishing date	2013-01-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1000976-0
ISSN	1099-1492 ; 0952-3480
ISSN (online)	1099-1492
ISSN	0952-3480
DOI	10.1002/nbm.2909
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