Egbe Vydaline Agbor Otu, Rozhkov Sergei, Sosa German, Mallikaratchy Prabodhika
Biochemistry, CUNY Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, United States.
Molecular, Cellular, and Developmental Biology, CUNY Graduate Center, The City University of New York, 365 Fifth Avenue, New York, NY 10016, United States.
Adv Drug Deliv Rev. 2025 Sep 7;226:115685. doi: 10.1016/j.addr.2025.115685.
Targeted drug delivery significantly enhances therapeutic efficacy across various diseases, particularly in cancer treatments, where conventional approaches such as chemotherapy and radiotherapy often cause severe side effects. In this context, nucleic acid aptamers-short, single-stranded DNA or RNA oligonucleotides capable of binding specific targets with high affinity-have emerged as promising tools for precision drug delivery and therapy. Aptamers can be selected against whole, living cells using SELEX and chemically modified for diverse applications. Their chemical versatility and specific binding capabilities allow aptamers to be engineered into aptamer-drug conjugates, nanoparticles, DNA origami structures, and bi-/multivalent or bispecific constructs. These platforms enable selective recognition of unique molecular signatures on cells or small molecules, facilitating highly targeted drug delivery and controlled release at the disease site. Such precision reduces systemic toxicity and enhances therapeutic outcomes. Compared to antibodies, aptamers offer several advantages, including faster tissue penetration, lower immunogenicity, greater chemical stability, and improved bioavailability in vivo. This review highlights recent advances in aptamer modification strategies-both covalent and non-covalent-for conjugation with chemotherapeutic agents, gold nanoparticles (GNPs), and photosensitizers. We further assess their potential as drug delivery vehicles and therapeutic agents and discuss how these innovations are driving progress in precision medicine.
靶向给药显著提高了针对各种疾病的治疗效果，尤其是在癌症治疗中，传统的化疗和放疗等方法往往会导致严重的副作用。在这种背景下，核酸适体——能够高亲和力结合特定靶点的短单链DNA或RNA寡核苷酸——已成为精准给药和治疗的有前途的工具。适体可以通过指数富集的配体系统进化技术（SELEX）针对完整的活细胞进行筛选，并进行化学修饰以用于多种应用。它们的化学多功能性和特异性结合能力使适体能够被设计成适体-药物偶联物、纳米颗粒、DNA折纸结构以及双价或双特异性构建体。这些平台能够选择性识别细胞或小分子上独特的分子特征，促进在疾病部位进行高度靶向给药和控释。这种精准性降低了全身毒性并提高了治疗效果。与抗体相比，适体具有几个优点，包括更快的组织穿透性、更低的免疫原性、更高的化学稳定性以及体内更好的生物利用度。本综述重点介绍了适体修饰策略（包括共价和非共价修饰）在与化疗药物、金纳米颗粒（GNP）和光敏剂偶联方面的最新进展。我们进一步评估了它们作为药物递送载体和治疗剂的潜力，并讨论了这些创新如何推动精准医学的发展。
