Journal of Biological Engineering最新文献

Recently, combination therapy has gotten more attention for some progressive therapeutic cancers. In in vivo studies, combination therapy requires better delivery, even though, in vitro studies, effective inhibition of various tumor cells has been identified due to uncontrolled ratiometric delivery. To target tumors with lipodisk nanoparticle formulations, this study established ratiometric loading and transport of cancer drugs such as paclitaxel (PTX) and salinomycin (SAL) on a single platform. Furthermore, including slightly pH-responsive peptides (PRPs) to lipodisks significantly improved cell and tumor-specific integration. The resulting lipodisks had a pH-sensitive characteristic of approximately 40 nm and were co-loaded. The ratiometric administration of two drugs through lipodisks was established in vitro in A549 and H1299 cells. Co-loaded lipodisks' synergistic drug ratio enhanced their cytotoxicity to tumor cells. Apoptosis in lung cancer A549 and H1299 cells is embedded in nanoparticles in biochemical models like nuclear DAPI staining and acridine orange/ethidium bromide (AO/EB). Cytotoxicity data on coloaded lipodisks in vitro can be used to predict their inhibitory activity and improve the clinical outcome of the synergistic treatment. Moreover, co-loaded lipodisks exhibit a high tumor inhibition after intravenous administration, which results in significant anticancer effects in H1299tumor-bearing mice with minimum damage to normal organs. Finally, this work presents a simple pH-responsive lipodisk nanoparticle platform for co-loaded drug delivery to improve therapeutic potential against lung cancer cells.

Human papillomavirus (HPV) is a major causative agent of cervical and other mucosal cancers. However, the distribution and accessibility of current prophylactic vaccines remain limited, especially in low- and middle-income countries (LMICs), due to high production costs, cold-chain dependency, and limited induction of mucosal immune responses. To addressing these challenges, we designed a rationally constructed multi-epitope HPV vaccine (HPV_MEV) incorporating conserved cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B-cell epitopes from diverse high- and low-risk HPV genotypes. The construct includes the Toll-like receptor 4 (TLR4) agonist RS09 to enhance innate immune activation and cholera toxin B subunit (CTB) as a mucosal adjuvant to facilitate uptake and presentation at mucosal surfaces. The codon-optimized gene was stably integrated into the chloroplast genome of Nicotiana tabacum via biolistic transformation. Molecular analyses confirmed site-specific integration, homoplasmy, and high-level antigen accumulation (~3.6 mg/g fresh weight; ~20.8% of total soluble protein). Immunogenicity was evaluated in BALB/c mice following intraperitoneal administration of purified antigen or oral gavage of lyophilized transplastomic leaf tissue. Oral administration induced antigen-specific systemic IgG and mucosal IgA responses, with higher levels of vaginal IgA observed compared with parenteral delivery, reflecting enhanced mucosal antibody induction. The chloroplast-produced HPV_MEV exhibited immunogenicity comparable to its E. coli-expressed counterpart, supporting its structural and functional integrity. Overall, this study demonstrates the feasibility of plastid biotechnology as a platform for producing a thermostable, orally deliverable HPV vaccine candidate and provides preliminary immunogenicity data supporting its application as a promising vaccine candidate for accessible vaccination strategies against HPV and other mucosally transmitted pathogens in resource-limited settings.