Ochoa-Sánchez Carlos, Rodríguez-León Ericka, Iñiguez-Palomares Ramón, Rodríguez-Beas César
Physics Department, Universidad de Sonora. Rosales and Luis Encinas 8300, Hermosillo, Sonora 83000, México.
ACS Omega. 2024 Nov 13;9(47):46664-46678. doi: 10.1021/acsomega.4c06714. eCollection 2024 Nov 26.
In recent decades, the development and application of nonviral vectors, such as liposomes and lipidic nanoparticles, for gene therapy and drug delivery have seen substantial progress. The interest in the physicochemical properties and structures of the complexes liposome/DNA and liposome/RNA is due to their potential to substitute viruses as carriers of drugs or genetic material into cells with minimal cytotoxicity, which could lead to their use in gene therapy. Initially, cationic liposomes were utilized as nonviral DNA delivery vectors; subsequently, different molecules, such as polymers, were incorporated to enhance transfection efficiency. Additionally, liposome/protein complexes have been developed as nonviral vectors for the treatment of diseases. The most relevant internalization pathways of these vectors and the few transfection results obtained using targeted and nontargeted liposomes are discussed below. The high cytotoxicity of cationic liposomes represents a significant challenge for the development of gene therapy and drug delivery. Anionic liposomes offer a promising alternative to address the limitations of conventional cationic liposomes, including immune response, short circulation time, and low toxicity. This review will discuss the advantages of cationic liposomes and the novel anionic liposome-based systems that have emerged as a result. The advent of novel designs and manufacturing techniques has facilitated the development of innovative systems, designated as lipid nanoparticles (LNPs), which serve as highly efficacious regulators of the immune system.
近几十年来,脂质体和脂质纳米颗粒等非病毒载体在基因治疗和药物递送方面的开发与应用取得了重大进展。对脂质体/DNA和脂质体/RNA复合物的物理化学性质及结构感兴趣,是因为它们有潜力替代病毒,以最小的细胞毒性将药物或遗传物质作为载体送入细胞,这可能促使其在基因治疗中得到应用。最初,阳离子脂质体被用作非病毒DNA递送载体;随后,加入了不同分子,如聚合物,以提高转染效率。此外,脂质体/蛋白质复合物已被开发为治疗疾病的非病毒载体。下文将讨论这些载体最相关的内化途径以及使用靶向和非靶向脂质体获得的少数转染结果。阳离子脂质体的高细胞毒性是基因治疗和药物递送发展面临的重大挑战。阴离子脂质体为解决传统阳离子脂质体的局限性提供了一种有前景的替代方案,这些局限性包括免疫反应、循环时间短和毒性低。本综述将讨论阳离子脂质体的优势以及由此出现的新型阴离子脂质体基系统。新型设计和制造技术的出现推动了创新系统的发展,即脂质纳米颗粒(LNPs),它们是高效的免疫系统调节剂。