Combination therapy of multiple drugs through a single system is exhibiting high therapeutic effects. We investigate nanocarrier mediated inhibitory effects of topotecan (TPT) and quercetin (QT) on triple negative breast cancer (TNBC) (MDA-MB-231) and multi drug resistant (MDR) type breast cancer cells (MCF-7) with respect to cellular uptake efficiency and therapeutic mechanisms as in vitro and in vivo. The synthesized mesoporous silica nanoparticle (MSN) pores used for loading TPT; the outer of the nanoparticles was decorated with poly (acrylic acid) (PAA)-Chitosan (CS) as anionic inner-cationic outer layer respectively and conjugated with QT. Subsequently, grafting of arginine-glycine-aspartic acid (cRGD) peptide on the surface of nanocarrier (CPMSN) thwarted the uptake by normal cells, but facilitated their uptake in cancer cells through integrin receptor mediated endocytosis and the dissociation of nanocarriers due to the ability to degrade of CS and PAA in acidic pH, which enhance the intracellular release of drugs. Subsequently, the released drugs induce remarkable molecular activation as well as structural changes in tumor cell endoplasmic reticulum, nucleus and mitochondria that can trigger cell death. The valuable CPMSNs may open up new avenues in developing targeted therapeutic strategies to treat cancer through serving as an effective drug delivery podium.
The
cargo-loaded mesoporous silica nanoparticles (MSNs) with convenient
surface modification can facilitate the development of the innovative
nanodrug system. Herein, the present investigation described the electrostatically
self-assembled MSNs as a nanosized drug carrier to realize potent
synergistic chemotherapy based on the specificity in targeting cytoplasm
and nucleus of tumor cells. In this context, the primarily constructed
MSNs were subjected with anticancer drug topotecan (TPT) into its
large pores. Then, the selective TAT peptide (a nuclear localization
signal peptide) was anchored onto TPT-loaded MSNs (TPT-MSN). Subsequently,
the positive surface of TPT-MSN-TAT was capped with negatively charged
components, poly(acrylic acid) (PAA)-cRGD peptide and citraconic anhydride
(CAH)-metformin (MT), and acted as a smart gatekeeper. Comparatively,
PAA-cRGD attached onto MSNs serving as the targeted molecules could
upsurge by invasion into cancer cells. Interestingly, the acidic pH
of the lysosomal compartment in tumor cells triggers the conjugated
CAH from the polymer decorated mesoporous silica (PMS) nanocomposite
and could efficiently release MT into the cytoplasm. Consequently,
the remaining TPT-MSN-TAT efficiently targets the nucleus and delivers
the TPT to improve synergistic chemotherapeutic effects. The precisely
released drugs were individually enhanced in the in vitro and in vivo cell killing efficiencies. Thus, the
study provides a potential drug delivery podium through combined drugs
to realize cancer cell targeting approach.
Today, the world population is facing an existential threat by an invisible enemy known as severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) or COVID-19. It is highly contagious and has infected a larger fraction of human population across the globe on various routes of transmission. The detailed knowledge of the SARS-CoV-2 structure and clinical aspects offers an important insight into the evolution of infection, disease progression and helps in executing the different therapies effectively. Herein, we have discussed in detail about the genome structure of SARS-CoV-2 and its role in the proteomic rational spread of different muted species and pathogenesis in infecting the host cells. The mechanisms behind the viral outbreak and its immune response, the availability of existing diagnostics techniques, the treatment efficacy of repurposed drugs and the emerging vaccine trials for the SARS-CoV-2 outbreak also have been highlighted. Furthermore, the possible antiviral effects of various herbal products and their extracted molecules in inhibiting SARS-CoV-2 replication and cellular entry are also reported. Finally, we conclude our opinion on current challenges involved in the drug development, bulk production of drug/vaccines and their storage requirements, logistical procedures and limitations related to dosage trials for larger population.
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