Nandy Urmica, Azad Mandal Abul Kalam
School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore Campus, Vellore 632014, India.
Centre for Nanobiotechnology, Vellore Institute of Technology, Vellore Campus, Vellore 632014, India.
ACS Appl Bio Mater. 2025 Aug 18;8(8):6676-6700. doi: 10.1021/acsabm.5c00968. Epub 2025 Aug 5.
Pancreatic cancer (PC), one of the most aggressive and lethal malignancies, remains an imminent threat to human health despite enormous advancements in cancer research. Traditional therapeutic approaches are unable to significantly enhance the life expectancy of PC patients due to limitations such as lower targetability, recurrence of cancerous tumors, and side effects on healthy cells. Nucleic acid therapeutics (NATs) offer a promising alternative against traditional approaches due to their ability to target and modify genetic pathways involved in PC progression, thus providing precision treatment. However, their efficient transportation to cancerous cells and tissues is still a major obstacle. Because of the high biocompatibility, tunable physicochemical characteristics, surface functionalization potential, and scalable manufacturing potential, nanomaterials have established themselves as a frontrunner as a delivery carrier against different diseases. Considering this, different nanocarriers were explored as a vehicle for anticancer therapeutics, especially to deliver therapeutic drugs, NATs, etc., and also provided a shield against enzymatic and chemical degradation in the bloodstream while promoting tumor-specific accumulation and targetability. Pertaining to this, in the current review, we have systematically discussed the development of nanomaterial-based NATs delivery systems for the delivery of nucleic acids like siRNA, miRNA, mRNA, saRNA, pDNA, CRISPR-Cas9 guide RNA, and other nucleic acids against PC, with an emphasis on their benefits, drawbacks, and translational potential. We also highlighted and compared the preclinical assessment of nanomaterial-mediated NATs delivery in PC therapy in wild-type and drug-resistant PC cells and discussed NATs delivery in two-dimensional (2D) and three-dimensional (3D) cell culture models alongside in vivo and clinical studies. Additionally, we also explored the possibilities of the 3D cell culture model's advantage over traditional 2D cell cultures and their relevance to in vivo systems, especially in facilitating NATs delivery and clinical translation possibilities, and paved the way for future research and clinical applications toward precision medicine.
胰腺癌（PC）是最具侵袭性和致命性的恶性肿瘤之一，尽管癌症研究取得了巨大进展，但它仍然对人类健康构成紧迫威胁。由于靶向性较低、癌性肿瘤复发以及对健康细胞的副作用等局限性，传统治疗方法无法显著提高PC患者的预期寿命。核酸疗法（NATs）因其能够靶向和修饰参与PC进展的遗传途径，从而提供精准治疗，为对抗传统方法提供了一种有前景的替代方案。然而，它们有效运输到癌细胞和组织仍然是一个主要障碍。由于具有高生物相容性、可调节的物理化学特性、表面功能化潜力和可扩展的制造潜力，纳米材料已成为针对不同疾病的递送载体的领跑者。考虑到这一点，人们探索了不同的纳米载体作为抗癌治疗药物的载体，特别是用于递送治疗药物、NATs等，还能在血液中提供针对酶促和化学降解的保护，同时促进肿瘤特异性积累和靶向性。与此相关的是，在当前的综述中，我们系统地讨论了基于纳米材料的NATs递送系统的发展，用于递送诸如siRNA、miRNA、mRNA、saRNA、pDNA、CRISPR-Cas9引导RNA等核酸以及其他针对PC的核酸，重点介绍了它们的优点、缺点和转化潜力。我们还强调并比较了纳米材料介导的NATs递送至野生型和耐药PC细胞的PC治疗中的临床前评估，并讨论了在二维（2D）和三维（3D）细胞培养模型中的NATs递送以及体内和临床研究。此外，我们还探讨了3D细胞培养模型相对于传统2D细胞培养的优势及其与体内系统的相关性，特别是在促进NATs递送和临床转化可能性方面，并为未来针对精准医学的研究和临床应用铺平了道路。
