About the lab
NNRL is involved in multidisciplinary research activities. Major areas include Nanomedicine, Nanotheranostics and molecular virology specifically Cancer Research and Infectious Diseases,
Featured projects (1)
Featured research (11)
We hereby propose the use of stable, biocompatible, and uniformly sized polymeric micelles as high-radiotracer-payload carriers at region-of-interest with negligible background activity due to no or low offsite radiolysis. We modified glycol chitosan (GC) polymer with varying levels of palmitoylation (P) and quaternization (Q). Quaternary ammonium palmitoyl glycol chitosan (GCPQ) with a Q:P ratio of 9:35 (Q9P35GC) offers >99% biocompatibility at 10 mg mL−1. Q9P35GC micelles exhibit >99% 99mTechnetium (99mTc) radiolabeling via the stannous chloride reduction method without heat. The 99mTc-Q9P35GC micelles (65 ± 3 nm) exhibit >98% 6 h serum stability at 37 °C and 7 day of radiochemical stability at 25 °C. HepG2 cells show a higher uptake of FITC-Q9P35GC than Q13P15GC and Q20P15GC. The in vivo 24 h organ cumulated activity (MBq h) order follows: liver (234.4) > kidneys (60.95) > GIT (0.73) > spleen (88.84). The liver to organ ratio remains higher than 2.4, rendering a better contrast in the liver. The radiotracer uptake decreases significantly in fibrotic vs. normal liver, whereas a blocking study with excess Q9P35GC significantly decreases the radiotracer uptake in a healthy vs. fibrotic liver. FITC-Q9P35GC shows in vivo hepato-specific uptake. Radiotracer liver uptake profile follows reversible binding kinetics with data fitting to two-tissue compartmental (2T), and graphical Ichise multilinear analysis (MA2) with lower AIC and higher R2 values, respectively. The study concludes that 99mTc-Q9P35GC can be a robust radiotracer for noninvasive hepatocyte function assessment and diagnosis of liver fibrosis. Furthermore, its multifunctional properties enable it to be a promising platform for nanotheranostic applications.
TNFα and NF-kB contribute in activation of pro-inflammatory signaling pathways and complications of coronary artery diseases (CAD). Current study highlights novel properties of Au (15 ± 2nm), ZnO (77± 45nm) and MgO (11± 4nm) nanoparticles (NPs) as possible anti-inflammatory agents with greater efficacy and lower toxicity. Decrease in TNFα and NF-kB levels in Single Vessel Disease (SVD), Double Vessel Disease (DVD) and Triple-Vessel coronary artery disease (TVD) macrophage and lymphocyte cultures at varying concentrations of NPs has been studied to find an effective therapeutic concentration (ETC). Au and MgO NPs exhibits 5µg/ml ETC compared to 1µg/ml ZnO in all three CAD categories with negligible toxicity. ZnO remains most statistically significant (p<0.001) in SVD and TVD cultures whereas MgO shows efficacy in DVD and TVD cultures with more than 50% reduction in TNFα and NF-kB levels at their respective ETCs. Au NPs exhibit prominent effect in DVD cultures. The mRNA expression results support the down-regulation of TNFα and NF-kB after NPs exposure in respective cultures. Findings of this prospective observational cohort study suggest use of NPs as an alternate anti-inflammatory agent in coronary artery and other diseases.
Purpose: Acinetobacter baumannii antibiotic resistant infections in high-risk patients are a great challenge for researchers and clinicians worldwide. In an effort to achieve potent bactericidal outcomes, a novel chitosan-mastoparan nanoconstruct (Mast-Cs NC) was designed and assessed for its therapeutic potential through in silico, in vitro and in vivo experimentation against clinical multidrug-resistant (MDR) A. baumannii. Methods: Optimized 3D structures of mastoparan and chitosan were coupled computationally through an ionic cross-linker to generate a circular ring of chitosan encasing mastoparan. The complex was assessed for interactions and stability through molecular dynamic simulation (MDS). Binding pocket analysis was used to assess the protease-peptide interface. Mast-Cs NC were prepared by the ionic gelation method. Mast-Cs NC were evaluated in vitro and in vivo for their therapeutic efficacy against drug-resistant clinical A. baumannii. Results: MDS for 100 ns showed stable bonds between chitosan and mastoparan; the first at chitosan oxygen atom-46 and mastoparan isoleucine carbon atom with a distance of 2.77 Å, and the second between oxygen atom-23 and mastoparan lysine nitrogen atom with a distance of 2.80 Å, and binding energies of -3.6 and -7.4 kcal/mol, respectively. Mast-Cs complexes approximately 156 nm in size, with +54.9 mV zeta potential and 22.63% loading capacity, offered >90% encapsulation efficiency and were found to be geometrically incompatible with binding pockets of various proteases. The MIC90 of Mast-Cs NC was significantly lower than that of chitosan (4 vs 512 μg/mL, respectively, p<0.05), with noticeable bacterial damage upon morphological analysis. In a BALB/c mouse sepsis model, a significant reduction in bacterial colony count in the Mast-Cs treated group was observed compared with chitosan and mastoparan alone (p<0.005). Mast-Cs maintained good biocompatibility and cytocompatibility. Conclusion: Novel mastoparan-loaded chitosan nanoconstructs signify a successful strategy for achieving a synergistic bactericidal effect and higher therapeutic efficacy against MDR clinical A. baumannii isolates. The Mast-Cs nano-drug delivery system could work as an alternative promising treatment option against MDR A. baumannii.
Background: Ajuga bracteosa is a traditional herb used against various diseases. Objective: Current research aimed to investigate the anti-diabetic and hepato-protective effect of green synthesized silver nanoparticles (ABAgNPs) using Ajuga bracteosa aqueous extract (ABaqu). Methods: In vitro anti-diabetic and cytotoxic effects were carried out via α- glucosidase inhibition, brine shrimp lethality, and protein kinase inhibition assays. For in vivo screening of 200 mg/kg and 400 mg/kg of both ABAgNPs and ABaqu in alloxan-induced and CCl4-induced Swiss albino mice were used. Liver and kidney functional markers, hematology, and histopathological studies were carried out after 14 days of administration. Results: In vivo antidiabetic and anti-cancerous effects showed valuable anti-hyperglycemic and hepato-protective potential when mice were treated with ABaqu and ABAgNPs. A significant reduction in the blood glucose level was recorded when ABaqu and ABAgNPs were administrated orally compared to Glibenclamide treated group. Significant reduction in ALT, AST, ALP, urea, uric acid, and creatinine was recorded in ABaqu and ABAgNPs treated diabetic mice. The hepato-protective findings indicated that ALT, ALP, AST were elevated in CCl4-induced mice while declined in both ABAgNPs and ABaqu treated CCl4-induced mice. Histopathological examination revealed that ABAgNPs have hepato-protective activity. Conclusion: It was concluded that ABAgNPs and ABaqu possessed strong anti-diabetic and hepato-protective phytoconstituents which could be used in the prevention of diseases.
Two of the limitations associated with cancer treatment are the low efficacy and the high dose-related side effects of anticancer drugs. The purpose of the current study was to fabricate biocompatible multifunctional drug-loaded nanoscale moieties for co-therapy (chemo-photothermal therapy) with maximum efficacy and minimum side effects. Herein, we report in vitro anticancerous effects of doxorubicin (DOX) loaded on gold nanorods coated with the polyelectrolyte poly(sodium-4-styrenesulfonate) (PSS-GNRs) with and without NIR laser (808 nm, power density = 1.5 W/cm ² for 2 min) irradiation. The drug-loading capacity of PSS-GNRs was about 76% with a drug loading content of 3.2 mg DOX/mL. The cumulative DOX release significantly increased after laser exposure compared to non-irradiated samples ( p < 0.05). The zeta potential values of GNRs, PSS-GNRs and DOX-PSS-GNRs were measured as 42 ± 0.1 mV, −40 ± 0.3 mV and 39.3 ± 0.6 mV, respectively. PSS-GNRs nanocomplexes were found to be biocompatible and showed higher photothermal stability. The DOX-conjugated nanocomplexes with NIR laser irradiation appear more efficient in cell inhibition (93%) than those without laser exposure (65%) and doxorubicin alone (84%). The IC 50 values of PSS-GNRs-DOX and PSS-GNRs-DOX were measured as 7.99 and 3.12 µg/mL, respectively, with laser irradiation. Thus, a combinatorial approach based on chemotherapy and photothermal strategies appears to be a promising platform in cancer management.
- NILOP Nanomedicines Research Laboratories (NNRL)
About Abida Raza
- Abida Raza, a nano-biochemist is among pioneer researchers in the field of Nanomedicine and founder of Nanotheranostic research in Pakistan. She heads NILOP Nanomedicine Research Laboratories (NNRL), National Institute of Lasers & Optronics. Abida does research in Cancer, Virology and Polymer Chemistry. Her current projects are 'Nanomedicine, Nanotheranostic and Virology.