Amrita Arup Roy, Naitik Jain, Rahul Pokale, Geethu Madhusoodanan, Anoushka Mukharya, Syeda Ayesha Farhana, Bola Sadashiva Satish Rao, Jayant Sastri Goda, Srinivas Mutalik
Messenger RNA (mRNA)-based therapeutics have revolutionised cancer immunotherapy by enabling transient, non-integrating expression of tumour antigens, cytokines, and immunomodulators. However, the inherent instability and immunogenicity of mRNA necessitate efficient delivery platforms led by lipid nanoparticles (LNPs). This review comprehensively discusses the evolution, design, and application of LNPs for mRNA and gene delivery in cancer immunotherapy. We explore their physicochemical properties, mechanisms of cellular uptake, endosomal escape, and immunogenic potential, alongside surface engineering strategies for tumour targeting. Special emphasis is placed on recent advances in LNP-based mRNA vaccines, CAR-T cell engineering, bispecific antibody delivery, and combinatorial therapies. The article synthesizes insights from preclinical studies, clinical trials, and scalable manufacturing innovations, including microfluidics and tangential flow filtration. Furthermore, we address storage stability, immunotoxicity, and regulatory hurdles that shape clinical translation. Together, these insights underscore LNPs as a transformative vehicle for next-generation mRNA cancer immunotherapies and highlight future directions in overcoming delivery and immune landscape barriers.