Transfection of Cancer Cells on 3D Engineered Extracellular Matrix Using Surface Capped Protein Nanoparticle Toward Effective Autologous Cell Therapy

Autologous cell therapy holds promising potential for personalized cancer treatment, contingent on rapid proliferation and efficient genetic transfection of patient-derived cancer cells. Our prior research capitalized on a three-dimensional engineered extracellular matrix (3D eECM) to foster cell growth. However, traditional electroporation for gene delivery presents significant drawbacks, notably the reduction of cell viability and increased risk of gene mutation, resulting in a decreased number of desired modified therapeutic cells. Furthermore, the requirement for cell detachment from the 3D eECM during electroporation exacerbates cell loss and genetic instability.<br/>Addressing these challenges, we propose an advanced transfection approach utilizing surface-capped protein nanoparticles that are prepared through an electrohydrodynamic jetting process and capped with a polymeric material. This method transcends the constraints of electroporation by enabling direct gene delivery to cells on the 3D eECM, ensuring cell viability and optimizing transfection efficacy, resulting in a high number of desired modified therapeutic cells. By obviating the need for cell detachment, we maintain the integrity of the proliferative milieu provided by the eECM and minimize the risk of gene alterations. Our innovative strategy holds the potential to enhance the viability and genetic stability of therapeutic cells, representing a significant advancement in the application of autologous cell therapy for cancer treatment.