The enhanced permeability and retention effect allows for passive targeting of solid tumours by nanoparticles carrying anticancer drugs. However, active targeting by incorporation of various ligands onto nanoparticles can provide for a more selective and enhanced chemotherapeutic effect and complement the deficiencies of the passive targeting approach. Here we report on the design of the carboxyl-terminated PEGylated gold nanoparticles (AuNPs), their functionalization with anti-CD133 monoclonal antibody (mAb) via a crosslinking reaction, and subsequent 5-fluorouracil (5-FU) drug loading. The synthesized products in the form of stable colloids were characterised using a range of physicochemical techniques, including X-ray diffraction (XRD), UV-Vis spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering (DLS). Conjugation of anti-CD133 mAb onto PEGylated AuNPs was confirmed with the use of UV-Vis, BCA protein assay and fluorescence microscopy. HCT116 colorectal cancer cells abundantly expressed CD133: 92.4 ± 1.3%, as measured by flow cytometry. Whereas PEGylated AuNPs not conjugated with anti-CD133 mAb accumulated mainly at the cellular membrane, nanoparticles conjugated with anti-CD133 mAb were contained within the nuclear region of the cells. Anti-CD133 mAb conjugation facilitated the specific intracellular uptake due to specific antigen-antibody binding interaction. In vitro cytotoxicity studies on HCT116 cells showed that PEGylated AuNPs and PEGylated AuNPs-CD133 did not elicit any toxicity at any of the tested concentrations. Meanwhile, 5-FU-PEGylated AuNPs-CD133 significantly reduced the cell viability relative to the treatment with 5-FU-PEGylated AuNPs without anti-CD133 mAb conjugates (p < 0.0001). This study shows that the conjugation of nanocarriers with the anti-CD133 antibody improves the specific targeting of 5-FU against colorectal cancer cells. These results demonstrate that simultaneous functionalisation of PEGylated AuNPs with antibodies and chemotherapeutic drugs is a viable strategy to combat cancer through targeted drug delivery.
Unlike pandemics in the past, the outbreak of coronavirus disease 2019 (COVID-19), which rapidly spread worldwide, was met with a different approach to control and measures implemented across affected countries. The lack of understanding of the fundamental nature of the outbreak continues to make COVID-19 challenging to manage for both healthcare practitioners and the scientific community. Challenges to vaccine development and evaluation, current therapeutic options, convalescent plasma therapy, herd immunity, and the emergence of reinfection and new variants remain the major obstacles to combating COVID-19. This review discusses these challenges in the management of COVID-19 at length and highlights the mechanisms needed to provide better understanding of this pandemic.
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which emerged in December 2019 and caused the coronavirus disease 2019 (COVID-19) pandemic, took the world by surprise with an unprecedented public health emergency. Since this pandemic began, extraordinary efforts have been made by scientists to understand the pathogenesis of COVID-19, and to fight the infection by providing various preventive, diagnostic and treatment opportunities based on either novel hypotheses or past experiences. Despite all the achievements, COVID-19 continues to be an accelerating health threat with no specifically approved vaccine or therapy. This review highlights the recent advances in COVID-19 infection, with a particular emphasis on nanomedicine applications that can help in the development of effective vaccines or therapeutics against COVID-19. A novel future perspective has been proposed in this review based on utilizing polymersome nano-objects for effectively suppressing the cytokine storm, which may reduce the severity of COVID-19 infection.