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Fulltext Boronic-Acid-Modified Nanomaterials for Biomedical Applications

Aung YY, Kristanti AN, Lee HV, Fahmi MZ

ACS Omega, 2021 Jul 20;6(28):17750-17765.
PMID: 34308011 DOI: 10.1021/acsomega.1c01352

Boronic-acid-modified nanomaterials have inspired significant research interest owing to their unique biocompatibility and excellent reversible interaction with diol groups containing saccharides, protein, DNA, and other related glucose compounds. However, the different sources and methods change the application of nanomaterials. Thus, surface-functionalized nanomaterials are of interest as one of the best ways to improve the application of the biomedical field. In this mini-review, we summarize recent studies on boronic-acid-modified nanomaterials, based on the carbon dot group and graphene oxides, which have been used in the fields of bioimaging, biosensing, antiviral inhibitors, etc. Moreover, the multivalent interaction on boronic-acid-modified materials has become the main key improvement for targeting treatment in the future. We mainly focused on any previously reported papers for synergistic future opportunities of superior biomedical applications of carbon dots (CDs) in the management and diagnostics of nanomedicine fields.
The antifungal agent of silver nanoparticles activated by diode laser as light source to reduce C. albicans biofilms: an in vitro study

Astuti SD, Puspita PS, Putra AP, Zaidan AH, Fahmi MZ, Syahrom A, et al.

Lasers Med Sci, 2019 Jul;34(5):929-937.
PMID: 30413898 DOI: 10.1007/s10103-018-2677-4

Candida albicans is a normal flora caused fungal infections and has the ability to form biofilms. The aim of this study was to improve the antifungal effect of silver nanoparticles (AgNPs) and the light source for reducing the biofilm survival of C. albicans. AgNPs were prepared by silver nitrate (AgNO3) and trisodium citrate (Na3C6H5O7). To determine the antifungal effect of treatments on C. albicans biofilm, samples were distributed into four groups; L + P+ was treatment with laser irradiation and AgNPs; L + P- was treatment with laser irradiation only; L - P+ was treatment with AgNPs only (control positive); L - P- was no treatment with laser irradiation or AgNPs (control negative). The growth of fungi had been monitored by measuring the optical density at 405 nm with ELISA reader. The particle size of AgNPs was measured by using (particle size analyzer) and the zeta potential of AgNPs was measured by using Malvern zetasizer. The PSA test showed that the particle size of AgNPs was distributed between 7.531-5559.644 nm. The zeta potentials were found lower than - 30 mV with pH of 7, 9 or 11. The reduction percentage was analyzed by ANOVA test. The highest reduction difference was given at a lower level irradiation because irradiation with a density energy of 6.13 ± 0.002 J/cm2 resulted in the biofilm reduction of 7.07 ± 0.23% for the sample without AgNPs compared to the sample with AgNPs that increased the biofilm reduction of 64.48 ± 0.07%. The irradiation with a 450-nm light source had a significant fungicidal effect on C. albicans biofilm. The combination of light source and AgNPs provides an increase of biofilm reduction compared to the light source itself.
Fulltext Review of Functional Aspects of Nanocellulose-Based Pickering Emulsifier for Non-Toxic Application and Its Colloid Stabilization Mechanism

Teo SH, Chee CY, Fahmi MZ, Wibawa Sakti SC, Lee HV

Molecules, 2022 Oct 23;27(21).
PMID: 36363998 DOI: 10.3390/molecules27217170

In the past few years, the research on particle-stabilized emulsion (Pickering emulsion) has mainly focused on the usage of inorganic particles with well-defined shapes, narrow size distributions, and chemical tunability of the surfaces such as silica, alumina, and clay. However, the presence of incompatibility of some inorganic particles that are non-safe to humans and the ecosystem and their poor sustainability has led to a shift towards the development of materials of biological origin. For this reason, nano-dimensional cellulose (nanocellulose) derived from natural plants is suitable for use as a Pickering material for liquid interface stabilization for various non-toxic product formulations (e.g., the food and beverage, cosmetic, personal care, hygiene, pharmaceutical, and biomedical fields). However, the current understanding of nanocellulose-stabilized Pickering emulsion still lacks consistency in terms of the structural, self-assembly, and physio-chemical properties of nanocellulose towards the stabilization between liquid and oil interfaces. Thus, this review aims to provide a comprehensive study of the behavior of nanocellulose-based particles and their ability as a Pickering functionality to stabilize emulsion droplets. Extensive discussion on the characteristics of nanocelluloses, morphology, and preparation methods that can potentially be applied as Pickering emulsifiers in a different range of emulsions is provided. Nanocellulose's surface modification for the purpose of altering its characteristics and provoking multifunctional roles for high-grade non-toxic applications is discussed. Subsequently, the water-oil stabilization mechanism and the criteria for effective emulsion stabilization are summarized in this review. Lastly, we discuss the toxicity profile and risk assessment guidelines for the whole life cycle of nanocellulose from the fresh feedstock to the end-life of the product.
Fulltext In Vitro Assessment on Designing Novel Antibiofilms of Pseudomonas aeruginosa Using a Computational Approach

Rachmawati D, Fahmi MZ, Abdjan MI, Wasito EB, Siswanto I, Mazlan N, et al.

Molecules, 2022 Dec 15;27(24).
PMID: 36558064 DOI: 10.3390/molecules27248935

An anti-biofilm that can inhibit the matrix of biofilm formation is necessary to prevent recurrent and chronic Pseudomonas aeruginosa infection. This study aimed to design compounds with a new mechanism through competitive inhibitory activity against phosphomannomutase/phosphoglucomutase (PMM/PGM), using in vitro assessment and a computational (in silico) approach. The active site of PMM/PGM was assessed through molecular redocking using L-tartaric acid as the native ligand and other small molecules, such as glucaric acid, D-sorbitol, and ascorbic acid. The docking program set the small molecules to the active site, showing a stable complex formation. Analysis of structural similarity, bioavailability, absorption, distribution, metabolism, excretion, and toxicity properties proved the potential application of ligands as an anti-biofilm. In vitro assessment with crystal violet showed that the ligands could reach up to 95.87% inhibition at different concentrations. The nitrocellulose membrane and scanning electron microscopic visualization showed that the untreated P. aeruginosa biofilm was denser than the ligand-treated biofilm.
Bio-based Pickering emulsifier from mangosteen residues-derived sodium caseinate grafted spherical cellulose nanocrystals: Stability, rheological properties and microstructure studies

Yahya M, Sakti SCW, Fahmi MZ, Chuah CH, Lee HV

Int J Biol Macromol, 2024 Feb;257(Pt 2):128696.
PMID: 38072349 DOI: 10.1016/j.ijbiomac.2023.128696

This study focuses on the preparation of mangosteen rind-derived nanocellulose via green ascorbic acid hydrolysis. Subsequently, milk protein-grafted nanocellulose particles were developed as a renewable Pickering emulsifier for water-oil stabilization. The stabilizing efficiency of modified nanocellulose (NC-S) at different caseinate (milk protein) concentrations (1.5, 3.0, and 4.0 % w/v) was tested in a water-in-oil emulsion (W/O ratio of 40:60). At a concentration 3.0 % w/v of caseinate (3.0NC-S), the emulsion exhibited a stronger network of adsorption between water, Pickering emulsifier, and oil. This resulted in reduced oil droplet flocculation, increased stability over a longer period, and favorable emulsifying properties, as depicted in the creaming index profile, oil droplet distribution, and rheology analysis. Since 3.0NC-S demonstrated the best colloidal stability, further focus will be placed on its microstructural properties, comparing them with those of mangosteen rind (MG), cellulose, and nanocellulose (NC-L). The XRD profile indicated that both NC-L and NC-S possessed a cellulose nanocrystal structure characterized as type I beta with a high crystallinity index above 60 %. Morphology investigation shown that the NC-L present in the spherical shape of particles with nanosized ranging at diameters of 11.27 ± 0.50 nm and length 11.76 ± 0.46 nm, while modified NC-S showed increase sized at 14.26 ± 4.60 nm and length 14.96 ± 4.94 nm. The increment of particle sizes from NC-L to NC-S indicated 2.82 × 10-15 mg/m2 of surface protein coverage by caseinate functional groups.
Breast Cancer Chemoprevention from Nano Zingiber officinale Roscoe

Wardana AP, Kristanti AN, Aminah NS, Fahmi MZ, Raoov M, Indriani

Int J Nanomedicine, 2024;19:11039-11053.
PMID: 39502639 DOI: 10.2147/IJN.S474611

BACKGROUND: After cardiovascular disease, cancer is one of the leading causes of death due to uncontrolled cell growth. Breast cancer is among the most prevalent types of cancer. Zingiber officinale Roscoe. rich in phenolic compounds, which can stimulate and function as endogenous antioxidants.
PURPOSE: Investigation of the in vivo chemopreventive has the potential of nano Z. officinale Roscoe (Zo-NPs) in breast cancer.
STUDY DESIGN: Using female Mus musculus Balb/c induced with benzo[α]pyrene, the chemopreventive action of Z. officinale Roscoe. nanoencapsulated using κ-carrageenan was assessed.
RESULTS: Z. officinale Roscoe Extract. contains 58 compounds, with the main component being [6]-gingerol with [6]-gingerol content being 697.65 ± 8.52 mg/g extract. Nanoencapsulation of Z. officinale Roscoe. has been successfully prepared with a particle size of 483.30 ± 11.23 nm. Zo-NPs are generally resistant to pH, temperature, and salt content variations. Compared to group C1, which underwent ductular dilatation, the administration of Zo-NPs (group T2) to female Mus musculus Balb/c, induced by benzo[α]pyrene, revealed no histological alterations in breast tissue. Moreover, administering Zo-NPs can raise blood serum levels of CAT, GSH, and SOD. In addition, it showed a greater ability to lower TNF-α levels than the T1 group, which received Z. officinale Roscoe extract. (Zo).
Fulltext Selectively mixed matrix hemodialysis membrane for adequate clearance of p-cresol by the incorporation of imprinted zeolite

Raharjo Y, Ismail AF, Dzarfan Othman MH, Fahmi MZ, Saiful, Santoso D, et al.

RSC Adv, 2023 Jan 18;13(5):2972-2983.
PMID: 36756405 DOI: 10.1039/d2ra07557a

The adequacy in uremic toxin removal upon hemodialysis treatment is essential in patients with kidney failure diseases as poor removal leads to heart failure, hypertension, and stroke. The combination of adsorption and diffusion processes has become very advantageous for hemodialysis membranes. By this mechanism, water-soluble uremic toxins (WSUTs) and protein-bounded uremic toxins (PBUTs) could be removed at one time. Therefore, this study aimed to develop a novel imprinted zeolite by p-cresol (IZC) and then incorporated it into polyethersulfone (PES) and poly(vinyl pyrrolidone) (PVP) to produce hollow fiber mixed matrix membrane (HF-MMM). The IZC proved to be sensitive in attracting the adsorbate, classifying it as having a strong adsorption behavior. Accordingly, IZC is very promising to be applied as an adsorbent in the hemodialysis treatment. In this study, IZC as p-cresol's adsorbent was incorporated into a PES-based polymeric membrane with a small addition of PVP to produce HF-MMM using a dry/wet spinning process. The effect of air gap distance between the spinneret and coagulant bath and percentage loading for PES, PVP, and IZC were studied and optimized to obtain the best performance of HF-MMM. The 40 cm of air gap distance, 16 wt% of PES, 2 wt% of PVP, and 1 wt% of IZC loading were able to produce a superior hemodialysis membrane. These optimized parameters showed sufficient uremic toxin removal, i.e., 60.74% of urea, 52.35% of p-cresol in the phosphate buffer saline solution, and 66.29% of p-cresol in bovine serum albumin solution for 4 h permeation using the dialysis system. These HF-MMMs also achieved pure water flux of 67.57 L m-2 h-1 bar-1 and bovine serum albumin rejection of 95.05%. Therefore, this membrane has proven to be able to clean up WSUT and PBUT through a one-step process. Moreover, as compared to the neat PES membrane, MMM was able to remove p-cresol at 186.22 times higher capability.
Fulltext In vivo Study of Chalcone Loaded Carbon Dots for Enhancement of Anticancer and Bioimaging Potencies

Fahmi MZ, Aung YY, Ahmad MA, Kristanti AN, Sakti SCW, Arjasa OP, et al.

Nanotheranostics, 2023;7(3):281-298.
PMID: 37064612 DOI: 10.7150/ntno.80030

The fluorescent imaging and drug delivery utilizing carbon dots nanomaterials (CDs) have attracted tremendously due to their unique optical ability and outstanding biocompatibility. Herein, we reported a new design of chalcone-loaded carbon dots (Chalcone-APBA-CDs) to serve chalcone transport onto cancer cells and enhance the CDs bioimaging and antitumor activity. The boronic acid was directly introduced to carbon dots (CDs) via pyrolysis process to drive CDs specifically to the cancer cell, and chalcone was mediated on CDs by ultrasonication to perform facile release of the drug delivery model. The successfully synthesized Chalcone-APBA-CDs were proved by their chemical structure, fluorescent activities, in vitro and in vivo analyses, and drug release systems using different pH. In addition, flow cytometry and confocal fluorescent imaging proved CDs' cellular uptake and imaging performance. In vitro analyses further proved that the Chalcone-APBA-CDs exhibited a higher toxicity value than bare CDs and efficiently inhibited the proliferation of the HeLa cells depending on their dose-response. Finally, the performance of Chalcone-APBA-CDs on cancer healing capability was examined in vivo with fibrosarcoma cancer-bearing mice, which showed a remarkable ability to reduce the tumor volume compared with saline (control). This result strongly suggested that the Chalcone-APBA-CDs appear promising simultaneously as cancer cell imaging and drug delivery.
Fulltext Unraveling In vivo Potential of Curcumin-loaded Graphene Quantum Dots on Drug Delivery and Release Kinetics Aspects of Cancer Treatment

Fahmi MZ, Sugito SFA, Wibrianto A, Novania S, Widyastuti S, Ahmad MA, et al.

Nanotheranostics, 2024;8(4):521-534.
PMID: 39507106 DOI: 10.7150/ntno.96559

This study introduces an innovative magnetic-based multifunctional anti-cancer drug carrier aiming to enhance the efficacy of curcumin in cancer therapy. The research investigates the potential of Graphene Quantum Dots (GQDs) as a curcumin drug delivery system for inhibiting in vivo cancer growth. GQDs with a particle diameter below 10 nm were synthesized via hydrothermal and Hummers methods, exhibiting homogeneity and crystalline structure according to AFM and XRD analyses. FTIR analysis confirmed functionalization success, revealing the formation of bonds between GQDs and curcumin. The optical properties of GQDs were assessed using a UV-Vis spectrophotometer and spectrofluorometer, resulting in vigorous fluorescence with a quantum yield of 1.32%. Subsequently, loading curcumin onto GQDs (CQDs/cur) resulted in an efficient system for delivering the anti-cancer drug, demonstrating significant in vivo efficacy. It was indicated by reduced tumor diameter and increased body weight in mice. Furthermore, the release kinetics of curcumin from GQDs were analyzed using the Peppas-Sahlin equation under varying pH conditions (4, 7, and 9), revealing the highest release rate in acidic conditions. In conclusion, this study highlights the potential of GQDs as highly efficient carriers for targeted curcumin delivery, showcasing promising prospects in cancer treatment.
Three-dimensional Au-MnO2 nanostructure as an agent of synergistic cancer therapy: chemo-/photodynamic and photothermal approaches

Sugito SFA, Wibrianto A, Chang JY, Fahmi MZ, Khairunisa SQ, Sakti SCW, et al.

Dalton Trans, 2024 Jul 09;53(27):11368-11379.
PMID: 38896134 DOI: 10.1039/d4dt01123f

The design of multimodal cancer therapy was focused on reaching an efficient process and minimizing harmful effects on patients. In the present study, the Au-MnO2 nanostructures have been successfully constructed and produced as novel multipurpose photosensitive agents simultaneously for photodynamic therapy (PDT), photothermal therapy (PTT), and chemodynamic therapy (CDT). The prepared AuNPs were conjugated with MnO2 NPs by its participation in the thermal decomposition process of KMnO4 confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy (FT-IR). The 16.5 nm Au-MnO2 nanostructure exhibited an absorbance at 438 nm, which is beneficial for application in light induction therapy due to the NIR band, as well as its properties of generating reactive oxygen species (ROS) associated with the 808 nm laser light for PDT. The photothermal transduction efficiency was calculated and compared with that of the non-irradiated nanostructure, in which it was found that the 808 nm laser induced a high efficiency of 83%, 41.5%, and 37.5% for PDT, PTT, and CDT, respectively. The results of DPBF and TMB assays showed that the efficiency of PDT and PTT was higher than that of CDT. The nanostructure also confirmed the time-dependent peroxidase properties at different H2O2, TMB, and H2TMB concentrations, promising good potency in applying nanomedicine in clinical cancer therapy.

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