RESUMEN
Chemotherapy and immunotherapy are two important modalities in cancer management. However, due to multiple reasons, a monotherapy is only partially effective. Hence, if used concurrently in targeted and stimuli-responsive manner, it could have been superior therapeutically. To facilitate co-delivery of chemotherapeutic and immunotherapeutic agent to the target cancer cells, engineered nanoparticles, i.e., a pH-responsive polymer PLGA-coated magnetic silica nanoparticles (Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs) encapsulating paclitaxel (PTX) and siRNA against programmed cell death ligand-1 (PD-L1) are synthesized and characterized. Developed nanoparticles demonstrated pH-sensitive sustained drug release up to 10 days. In vitro 4T1 cell line studies showed efficient cellular uptake, PD-L1 gene downregulation, and apoptosis. Further, in vivo efficacy studies carried out in the mice model demonstrated a significant reduction of tumor growth following treatment with dual-Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs as compared with monotherapy with Fe3O4-SiO2-PLGA-PDA-PTX NPs. The high therapeutic efficacy observed with dual-Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs was mainly due to the cytotoxic effect of PTX combined with targeted silencing of the gene of interest, i.e., PD-L1, which in turn improve CD8+ T cell-mediated cancer cell death as evident with increased proliferation of CD8+ T cells in co-culture experiments. Thereby, dual-Fe3O4-SiO2-PLGA-PDA-PTX-siRNA NPs may have a promising anti-cancer treatment potential against breast cancer; however, the beneficial effects of dual loading of PTX + PD-L1 siRNA may be corroborated against other cancer models such as lung and colorectal cancer models as well as in clinical trials.
RESUMEN
Streptococcus pneumoniae having almost 98 serotypes and being common cause of acute otitis media, pneumonia, bacteremia, meningitis etc., which results in high mortality and morbidity globally. Although vaccines like PCV-13 and PPV-23 are available, some problems like serotype replacement and poor immunogenicity in children, old age and immunocompromised people has been observed. To overcome these drawbacks protein/peptide-based vaccine can be a good strategy as these provides wide serotype coverage. However, immunogenicity of protein subunit vaccines is lower, that issue can be solved by using adjuvants. Recently nanoparticles as an adjuvant for vaccine delivery being used, which has provided not only good immunogenicity but also improved delivery and efficiency of protein-based vaccines. In this review we have discussed the latest advancement of nanoparticles-based protein/peptide vaccine delivery for Streptococcus pneumoniae.