Cancer immunotherapy increasingly relies on nucleic acid-based vaccines, yet achieving efficient and safe delivery remains a critical limitation. Polyplexes—electrostatic complexes of cationic polymers and nucleic acids—have emerged as versatile carriers offering greater chemical tunability and multivalent targeting capacity compared to lipid nanoparticles, with lower immunogenicity than viral vectors. This review summarizes key design principles governing polyplex performance, including polymer chemistry, architecture, and assembly route—emphasizing microfluidic fabrication for improved size control and reproducibility. Mechanistically, effective systems support stepwise delivery: tumor targeting, cellular uptake, endosomal escape (via proton-sponge, membrane fusion, or photochemical disruption), and compartment-specific cargo release. We discuss therapeutic applications spanning plasmid DNA, siRNA, miRNA, mRNA, and CRISPR-based editing, highlighting preclinical data across multiple tumor types and early clinical evidence of on-target knockdown in human cancers. Particular attention is given to physiological barriers and engineering strategies—including size-switching systems, charge-reversal polymers, and tumor-penetrating peptides—that improve intratumoral distribution. However, significant challenges persist, including cationic toxicity, protein corona formation, manufacturing variability, and limited clinical responses to date. Current evidence supports polyplexes as a modular platform complementary to lipid nanoparticles in selected oncology indications, though realizing this potential requires continued optimization alongside rigorous translational development.

Introduction: Lymph node status is a key prognostic factor of lung cancer. Although video-assisted thoracoscopic surgery (VATS) is widely used for early-stage disease, its consistency in achieving thorough lymph node dissection remains debated. While many studies show outcomes comparable to thoracotomy, others question its reliability for accurate staging in advanced cases. This study compared the oncologic efficacy of VATS and thoracotomy in pulmonary adenocarcinoma, focusing on lymph node dissection and postoperative outcomes. Materials and Methods: A retrospective analysis was conducted on 111 consecutive patients who underwent curative-intent resection for pulmonary adenocarcinoma between 2019 and 2023 at the “Prof. Dr. Alexandru Trestioreanu” Oncological Institute, 52 undergoing thoracotomy and 59 Video-Assisted Thoracoscopic Surgery (VATS). Results: Demographic and clinical characteristics were comparable between groups. Compared with thoracotomy, VATS was associated with a significantly higher number of harvested lymph nodes at stations 7 and 10. No significant differences between groups in the number of positive lymph nodes, postoperative morbidity, or 30-day mortality were observed. Conclusions: VATS appears to provide comparable lymph node retrieval and short-term outcomes to open surgery. These findings add valuable data from an underrepresented Eastern European population and support the broader adoption of minimally invasive techniques in lung cancer surgery.

Background and Objectives: The benefit of lobe-specific lymph node dissection (LS-LND) in non-small cell lung cancer (NSCLC) remains debated, especially in early-stage disease. Previous reviews often included all stages, leaving a gap in focused evaluations of clinical stage IA–IB NSCLC. This systematic review, supplemented by our institutional experience, aimed to compare overall survival (OS), recurrence-free survival (RFS), and postoperative complications between LS-LND and systematic lymph node dissection (S-LND) in clinical stage IA–IB NSCLC. Methods: We retrospectively reviewed 24 patients treated at our institution (14 S-LND vs. 10 LS-LND). Data on patient demographics, operative details, OS, RFS, and postoperative complications were collected. Risk of bias was assessed using established methodological tools. A targeted literature search was conducted in PubMed, EMBASE, and Web of Science from inception to 14 April 2022. Only three articles (total n = 1101 patients) met inclusion criteria focusing on clinical stage IA–IB NSCLC who underwent curative-intent resection. Results: LS-LND demonstrated comparable or slightly improved 5-year OS (range: 69.7–96.7%) versus S-LND (64.9–92.0%), and similar or slightly higher RFS (66.0–95.6% in LS-LND vs. 60.8–88.8% in S-LND). In our cohort, the 5-year OS was 78.6% in S-LND vs. 80.0% in LS-LND, and the 5-year RFS was 71.4% vs. 70.0%, respectively. Postoperative complications such as arrhythmias were less frequent in LS-LND groups overall. Our data showed a low rate of pneumonia in S-LND compared to LS-LND (7.1% vs. 10.0%); however, arrhythmias accounted for 14.3% in S-LND vs. 10.0% in LS-LND). Conclusions: For clinical stage IA–IB NSCLC, LS-LND offers oncologic outcomes that are comparable to S-LND, with a potential for reduced postoperative complications. The findings from our institution align with these trends observed in the literature. While these results suggest potential advantages of lobe-specific approaches, definitive conclusions require further validation through larger, prospective randomized studies to confirm the clinical benefits of LS-LND in early-stage NSCLC.