Employing an active targeting method with monoclonal antibodies for chemotherapeutics-loaded nanocarriers represents a promising option to enhance the specific drug delivery and alleviate the detrimental effects of chemotherapeutic agents. Targeted delivery to the human epidermal growth factor receptor-2 (HER2), which is overexpressed in HER2+ lung cancerous cells, can be accomplished by conjugating nanoparticles with a monoclonal antibody (anti-HER2). We developed trastuzumab (TZ)-conjugated chitosan iodoacetamide (CsIA)-coated liposomal nanoparticles carrying SN-38 (TZ-SN-CsIA LNPs) as a lung-targeted delivery. CsIA was used to develop trastuzumab-clacked nanoparticles (TZ LNPs). The structure, physicochemical characteristics, SN-38 encapsulation, SN-38 release, and anticancer properties of the LNPs were established. The TZ LNPs were spherical, measuring around 77 nm in diameter, and exhibited a positive zeta potential
upon drug incorporation, the diameter of the TZ LNPs enlarged. A sustained, 24-h SN-38 release from the nanocarriers was accomplished. TZ LNPs demonstrated substantial cellular accumulation and markedly enhanced anticancer efficacy against HER2+ Calu-3 lung adenocarcinoma cancer cells compared to the drug solution and unconjugated LNPs. Consequently, TZ-SN-CsIA LNPs may be a potential nanocarrier for HER2+ lung cancer.