Table 2 An overview regarding potential applications, strengths, and weaknesses of recent studies
From: Steering the course of CAR T cell therapy with lipid nanoparticles
Sr | Author | Year | LNP/mRNA modifications | Methodological strategy | Applications | Strengths | Weakness | References |
|---|---|---|---|---|---|---|---|---|
1. | Veiga et al. | 2018 | Modified mRNA loaded LNPs combined with ASSET | Precision protein expression strategy in Ly6c+ inflammatory leukocytes | Targeted expression of interleukin 10 in Ly6c+ inflammatory leukocytes in IBD induced mice | Therapeutic alteration of gene expression in vivo | Cell specificity remains a challenge; limited to inflammatory leukocytes | [57] |
2. | Di et al. | 2022 | Firefly luciferase encoding mRNA loaded LNPs | Biodistribution and Luciferase expression levels by bioluminescence imaging and enzyme activity assays | Size dependent biodistribution of LNPs | Transgene expression was most prominent in the liver | Accumulation of large sized LNPs in liver; variable transfection efficiency in different organs; limited biodistribution data beyond liver and spleen | [58] |
3. | Álvarez‐Benedicto et al. | 2023 | SORT LNPs | In situ transfection | Simplified CAR T cell production | Increases overall survival in B-cell lymphoma models; reduces tumor metastasis to liver | No long-term safety profiling; off-target effects of LNPs | [59] |
4. | Patel et al. | 2022 | Substitution of 25% and 50% 7α-hydroxycholesterol for cholesterol into LNPs | Engineering a library of LNPs incorporating hydroxycholesterols | Describes an impact on mRNA delivery to T cells by leveraging endosomal trafficking mechanisms | Enhancing mRNA delivery to T cells, increased late endosome production, reduced presence of recycling endosome | No long-term effects or clinical scalability have been described | [60] |
5. | Qiu et al. | 2021 | Combinatorial synthetic LNPs with distinct chemical structures and properties | Development of bioreducible and biodegradable LNPs using Michael addition reaction | Vaccination, cancer immunotherapy, protein replacement therapy, genome editing | Successful clinical approval of mRNA vaccines and siRNA drug (ONPATTRO) by FDA | Need for specific, efficient, and safe delivery systems; challenges in clinical translation of mRNA-based therapies | [61] |
6. | Patel et al. | 2024 | Bile acid-containing LNPs | Incorporation of bile acids (cholic acid) without cholesterol | Gastrointestinal or immune cell delivery | Generalizability of cholic acid replacement | Optimization needed for large-scale production | [62] |
7. | Billingsley et al. | 2020 | Ionizable LNPs | Screening of a library of 24 ionizable LNPs, selection of top-performing LNP formulation (C14-4) | Potential enhancement of mRNA-based CAR T cell engineering, reduction of cytotoxicity compared to electroporation | LNPs deliver mRNA efficiently to primary human T cells and induce functional protein expression | Further investigations warranted on long-term effects, scalability, and efficiency | [63] |
8. | Zhang et al. | 2024 | One-component ionizable cationic LNPs | Standalone carriers, rational design of cationic lipids rich in secondary amines | Targeted mRNA delivery to spleen and T cells | Efficient mRNA delivery in vitro and in vivo | Investigation of long-term safety and efficacy are warranted | [64] |
9. | Wang et al. | 2023 | Comirnaty® | Biodistribution of PEGylated LNPs and blood clearance | Understanding immune responses to LNPs | Demonstrates time- and dose-dependency of LNP-induced anti-PEG antibodies | Limited to animal model, may not fully reflect human response. Need for human studies | [65] |
10. | Wang et al. | 2023 | Noncationic thiourea LNPs | Strong hydrogen bond interaction between thiourea groups of noncationic thiourea LNPs and phosphate groups of mRNAs | Potential for future mRNA delivery with good inflammatory safety profiles, high gene transfection efficiency, and spleen-targeting delivery for disease treatments | Simplified preparation technology, negligible inflammatory and cytotoxicity side effects, higher gene transfection efficiency in vitro and in vivo, spleen-targeting delivery ability | Further investigation warranted for long-term safety, scalability, and broader applicability beyond spleen targeting | [66] |