Browsing by Author "Munir, Iqra"

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Open Access
A microfluidics-assisted double-barreled nanobioconjugate synthesis ıntroducing aprotinin as a new moonlight nanocarrier protein: tested toward physiologically relevant 3d-spheroid models
(American Chemical Society, 2024-04-02) Nazir, Faiqa; Munir, Iqra; Yeşilöz, Gürkan
Proteins are promising substances for introducing new drug carriers with efficient blood circulation due to low possibilities of clearance by macrophages. However, such natural biopolymers have highly sophisticated molecular structures, preventing them from being assembled into nanoplatforms with manipulable payload release profiles. Here, we report a novel anticancer nanodrug carrier moonlighting protein, Aprotinin, to be used as a newly identified carrier for cytotoxic drugs. The Aprotinin-Doxorubicin (Apr-Dox) nanobioconjugate was prepared via a single-step microfluidics coflow mixing technique, a feasible and simple way to synthesize a carrier-based drug design with a double-barreled approach that can release and actuate two therapeutic agents simultaneously, i.e., Apr-Dox in 1:11 ratio (the antimetastatic carrier drug aprotinin and the chemotherapeutic drug DOX). With a significant stimuli-sensitive (i.e., pH) drug release ability, this nanobioconjugate achieves superior bioperformances, including high cellular uptake, efficient tumor penetration, and accumulation into the acidic tumor microenvironment, besides inhibiting further tumor growth by halting the urokinase plasminogen activator (uPA) involved in metastasis and tumor progression. Distinctly, in healthy human umbilical vein endothelial (HUVEC) cells, drastically lower cellular uptake of nanobioconjugates has been observed and validated compared to the anticancer agent Dox. Our findings demonstrate an enhanced cellular internalization of nanobioconjugates toward breast cancer, prostate cancer, and lung cancer both in vitro and in physiologically relevant biological 3D-spheroid models. Consequently, the designed nanobioconjugate shows a high potential for targeted drug delivery via a natural and biocompatible moonlighting protein, thus opening a new avenue for proving aprotinin in cancer therapy as both an antimetastatic and a drug-carrying agent.
Open Access
Investigating physical properties of hybrid hyaluronic acid and collagen compositions of GelMA microgels toward tissue engineering and organ-on-chip applications
(American Chemical Society, 2023-10-13) Çınar, Aslı Gizem; Munir, Iqra
Microgels are promising tools in biomedical sciences to be utilized as 3D cell culture scaffolds and cell-delivery or drug-delivery vehicles. Carrying the desired properties of hydrogels, they can be fabricated from various materials in different shapes and sizes. Additionally, due to their increased surface-to-volume ratio, they provide fast nutrient, waste, and species transport with altered solute–material interactions. Despite their micrometer size and the differentiated behaviors that come with these properties, the characterization methods utilized so far to investigate their physical and morphological properties are majorly carried out on their bulk versions, resulting in inaccurate estimates and somewhat missed information. Here, in this work, swelling, degradation, and morphological examination assays curated for microgels are proposed to reflect the actual behavior of microgels. Accordingly, gelatin methacryloyl, complemented with hyaluronic acid methacrylate and collagen to set an example of different types of polymer networks, was fabricated into microgels using a droplet microfluidic platform with in situ photopolymerization. An easy washing and drying process is proposed as a substitution for the harsh conditions of lyophilization for morphological analysis, resulting in a much more accurate picture of the porous structures. Swelling and enzymatic degradation assays, usually done by immersing a bulk hydrogel in a medium for an extended period, are substituted with swelling and degrading individual microgels in a custom-made platform that enables real-time, statistically significant data acquisition. Results showed that, due to their small size, swelling occurs in a matter of minutes, with different temporal profiles depending on the medium and microgel compositions, and enzymatic degradation takes place in a couple of hours with varying behaviors, changing due to the polymers, enzyme type, and concentration. Overall, this work highlights the necessity and importance of characterizing microgels in their respective sizes, hopefully advancing their utilization in microphysiological systems and biomedical applications.
Open Access
Novel size-tunable and straightforward ultra-small nanoparticle synthesis in a varying concentration range of glycerol as a green reducing solvent
(American Chemical Society, 2023-08-08) Munir, Iqra; Yeşilöz, Gürkan
Despite all the possibilities available so far for the synthesis of nanoparticles (NPs), synthesizing ultra-small (<10 nm) monodispersed particles is still demanding. Getting a particular size with a straightforward method is a trial-and-error approach. To explore this prospective, in the current study, we have introduced a protocol which offers a varying concentration range of glycerol to successfully generate the NPs of repeatable and consistent particle size in each synthesis, thus giving an alternative from lengthy tentative preparations and/or testing protocols. Since synthesizing controlled sized nanoparticles in aqueous medium is somewhat difficult as the balance of particle growth and nucleation is challenging to control, herein, we used a polyol method with glycerol both as a solvent medium as well as reducing species for silver nitrate, as an example model ion source, to execute the nanoparticle synthesis. In order to maintain the stability of the synthesized NPs, polyvinylpyrolidone (PVP) was added as a stabilizer. The synthesis, monodispersity, and stability were confirmed using techniques such as UV–vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and X-ray powder diffraction (XRD), while morphological analysis and ultra-small size validation were conducted using TEM, SEM, and AFM. Interestingly, in the various concentrations of glycerol solution used (10–100%), we have observed a tunable linear size range to obtain ultra-small nanoparticles (<10 nm) up to 60% glycerol, while further increasing the glycerol component increased the size approximately to ∼160 nm, providing tunable properties in this synthesis procedure. Hence, this study provides a distinct possibility to obtain ultra-small nanoparticles with a tunable size feature for further applications in numerous fields.
Open Access
One-step synthesis of ultrasmall nanoparticles in glycerol as a promising green solvent at room temperature using omega-shaped microfluidic micromixers
(ACS Publications, 2023-11-28) Jahangir, Robab; Munir, Iqra; Yeşilöz, Gürkan
Despite innovations in the synthesis protocol of nanoparticles (NPs), the size distribution and uniformity of particles still remain as crucial attributes. Homogeneous and rapid nucleation is a critical phenomenon to obtain monodisperse nanoparticles. Herein, we have carried out the synthesis of metal nanoparticles in a customized microfluidic (MF) chip, with 18 omega-shaped micromixers, by using glycerol as a promising green solvent and reducing agent at various concentrations (10-80%), and simultaneous comparison of the results from batch synthesis. Initially, mixing characterization for 10-80% glycerol was obtained by adjusting the Peclet (Pe) number. Further, the effect of the Pe number, time, and concentrations of polyvinylpyrrolidone, metal source, and glycerol on the NP size was investigated. Interestingly, the experimental findings depicted that by varying different parameters, the spherical nanoparticles with an average ultrasmall particle diameter of <2 nm were obtained at all glycerol concentrations (10-80%), as compared to batch synthesis (giving a yield of ∼10-fold larger particles). The mixing efficiency in this MF chip design was analyzed by using a fluorescent dye in glycerol, while the particle morphology and size were characterized by using dynamic light scattering, transmission electron microscopy, and ultraviolet-visible spectroscopy. Hence, compared to the conventional benchtop-assisted NP synthesis, this study unveils the significant effect of the microfluidic technique on the synthesis of ultrasmall and homogeneous nanoparticles in a single step, using an environmentally friendly solvent.
Open Access
An outline of contributing vaccine technologies for SARS CoV2 advancing in clinical and preclinical phase-trials
(Bentham Science Publishers, 2022-04-21) Naz, Sheikh Saba; Munir, Iqra
Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV2) is an RNA virus involving 4 structural and 16 non-structural proteins, and exhibiting high transmission potential and fatality. The emergence of this newly encountered beta coronavirus-SARS CoV2 has brought over 2 million people to death, and more than 10 billion people got infected across the globe as yet. Consequently, the global scientific community has contributed to the synthesis and design of effective immunization technologies to combat this virus. Objectives: This literature review was intended to gather an update on published reports of the vaccines advancing in the clinical trial phases or preclinical trials, to summarize the foundations and implications of contributing vaccine candidates inferring their impact in the pandemic repression. In addition, this literature review distinctly facilitates an outline of the overall vaccine effectiveness at current doses. Methods: The reported data in this review was extracted from research articles, review articles and patents published from January 2020 to July 2021, available on Google Scholar, Pubmed, Pubmed Central, Research Gate, Science direct, and Free Patent Online Database by using combination of keywords. Moreover, some information is retrieved from native web pages of vaccine manufacturing companies' due to progressing research and unavailability of published research papers. Conclusion: Contributing vaccine technologies include: RNA (Ribonucleic acid) vaccines, DNA (Deoxyribonucleic acid) vaccines, viral vector vaccines, protein-based vaccines, inactivated vaccines, viruses-like particles, protein superglue, and live-attenuated vaccines. Some vaccines are prepared by establishing bacterial and yeast cell lines and as self-assembling adenovirus- derived multimeric protein-based self-assembling nanoparticle (ADDOmer). On May 19, WHO has issued an emergency use sanction of Moderna, Pfizer, Sinopharm, AstraZeneca, and Covishield vaccine candidates on account of clinical credibility from experimental data.
Embargo
Unlocking nature’s potential: ferritin as a universal nanocarrier foramplified cancer therapy testing via 3d microtissues
(American Chemical Society, 2024-12-12) Munir, Iqra; Nazir, Faiqa; Yeşilöz, Gürkan
In the existing development of extensive drug screening models, 3D cell cultures outshine conventional 2D monolayer cells by closely imitating the in vivo tumor microenvironment. This makes 3D culture a more physiologically relevant and convenient system in the regime of preclinical drug testing. In the nanomedicinal world, nanoconjugates as nanocarriers are largely hunted due to their capability of precisely binding to target cells and distributing essential dosages of therapeutic drugs with enhanced safety profiles. Thus, for boosted drug availability, the evolution from conventional drug treatment to combination therapies and last switching to drug carriers has gained significant progression in cancer cure. In contrast to conventional engineered nanoparticles, herein, we successfully designed biomolecule (ferritin)-based drug nanoconjugates effective both as a single drug (valproic acid-VPA) and twin-drug (valproic acid/doxorubicin-Dox) carriers, which dramatically enhance the proficiency of the tumor therapeutic modality. To question the reported adjuvant drug property of VPA, we progressed utilizing at first VPA alone as an effective yet exclusive tumor therapy when delivered via some carrier molecule, in particular protein. Subsequently, we paralleled this comprehensive investigation output to compare and test the coloading strategy of drugs and observe the synergistic and/or additive behavior of VPA in conjugation with other anticancer agents (Dox) while given via a carrier molecule. To approach this, VPA and/or Dox molecules were encapsulated into the ferritin (F) cavity using a thermosensitive synthesis method by maintaining the temperature at 60 degrees C. The successful encapsulation of drugs in the protein nanocage was confirmed through various characterization techniques. The F-VPA/F-VPA-Dox nanoconjugates exhibited similar morphology and structural characteristics to the hollow ferritin cage and showed significant cytotoxicity than the naked drugs when tested on physiologically relevant 3D spheroid models. Precisely, our first designed carrier nanoconjugate, i.e., F-VPA, offered more than a 3-fold increased intratumoral drug concentration than free VPA and significantly suppressed tumor growth after a single-dose treatment. However, our second modeled carrier nanoconjugate, viz. F-VPA-Dox, revealed an extended median survival period and lesser toxicity when administered at a much more effective dose (similar to 3-5 mu M), in 3D tumor spheroid models of various cancer cell lines. All in all, importantly, ferritin nanoconjugates exhibited an enhanced tumor inhibition rate with a single-dose treatment, which further confirms the benefits of the active targeting property of these nanocarriers. Moreover, these nanocarriers also offer to deliver a significant dose of the therapeutic drug into tumor cells, alongside tremendous biocompatibility and safety profiles in numerous tumor 3D spheroid models.