{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:05:40Z","timestamp":1789981540924,"version":"4.0.1"},"reference-count":114,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Cancer immunotherapy is a transformative technology allowing for the elimination of malignant cells through immune system stimulation; however, the large-scale clinical application of adoptive cellular therapy technologies is limited due to difficulties in\n                    <jats:italic>ex vivo<\/jats:italic>\n                    immune cell engineering, high costs, and complicated manufacturing process. Recently,\n                    <jats:italic>in vivo<\/jats:italic>\n                    immune cell engineering was discovered as an emerging approach that allows for the genetic reprogramming of immune cells in patients, thus circumventing many problems inherent to traditional cellular therapy technologies. Breakthroughs in targeted drug delivery systems such as cell-penetrating peptides, antibody- and receptor-mediated delivery approaches, lipid nanoparticles (LNPs), polymeric drug carriers, and biomimetic delivery systems allow for the more effective selective delivery of messenger RNA (mRNA), clustered regularly interspaced short palindromic repeats (CRISPR)\/Cas gene editing systems, proteins, and other types of cargo to the target immune cells.\n                    <jats:italic>In vivo<\/jats:italic>\n                    immune cell engineering allows for the efficient generation of chimeric antigen receptor T-cells (CAR-T), CAR- natural killer (NK) cells, engineered macrophages, dendritic cells, and other immune cell types; moreover, transient and permanent immune reprogramming is achievable via vivo technologies. The present review discusses the biological barriers limiting immune cell-targeted delivery, including biodistribution, cellular uptake, intracellular transport, and endosomal escape of delivered drugs, and reviews the latest advancements in targeted delivery technologies addressing these obstacles. We also address the latest applications of\n                    <jats:italic>in vivo<\/jats:italic>\n                    immune cell engineering in hematological malignancies and solid tumors, including mRNA therapeutics, CRISPR-based genome editing, and advanced programmable immunotherapy technologies. Furthermore, we discuss unresolved issues related to the specificity of targeting, efficiency of drug delivery, safety of treatment, manufacturing processes, and regulation of\n                    <jats:italic>in vivo<\/jats:italic>\n                    immune engineering technologies and outline future opportunities arising from the integration of nanomedicine, synthetic biology, genome engineering, and artificial intelligence-assisted materials science.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2026.1936688","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:24:05Z","timestamp":1789979045000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted delivery platforms for in vivo immune cell engineering: emerging strategies for cancer immunotherapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Hari Krishnareddy","family":"Rachamala","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences","place":["Jacksonville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandeep","family":"Atla","sequence":"additional","affiliation":[{"name":"Texas A&M Drug Discovery Center and Department of Chemistry, College of Arts and Sciences, Texas A&M University","place":["College Station, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramcharan Singh","family":"Angom","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine and Sciences","place":["Jacksonville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"103459","DOI":"10.1016\/j.rechem.2026.103459","article-title":"Molecular design and therapeutic applications of polymeric nanoparticles for drug delivery: a comprehensive review","volume":"28","author":"Ahmed","year":"2026","journal-title":"Results Chem."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3897\/pharmacia.72.e173384","article-title":"Chimeric antigen receptor (CAR) T cell therapy: current landscape, challenges, and future horizons in hematologic and solid tumors","volume":"72","author":"Al-Hussaniy","year":"2025","journal-title":"Pharmacia"},{"key":"B3","doi-asserted-by":"publisher","first-page":"4937","DOI":"10.1016\/j.ymthe.2025.06.036","article-title":"Targeted in vivo delivery of genetic medicines utilizing an engineered lentiviral vector platform results in CAR T and NK cell generation","volume":"33","author":"Andorko","year":"2025","journal-title":"Mol. 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