Carbohydrate–lectin interactions and glycol-molecule-driven self-assembly are powerful yet challenging strategies to create supramolecular nanostructures for biomedical applications. Herein, we develop a modular approach of micellization with a small molecular mannosylated-calix[4]arene synthetic core, CA₄-Man3, to generate nano-micelles, CA₄-Man3-NPs, which can target cancer cell surface receptors and facilitate the delivery of hydrophobic cargo. The oligomeric nature of the calix[4]arene enables the dynamic self-assembly of calix[4]arene (CA₄), where an amphiphile, functionalized with mannose units (CA-glycoconjugates) in the upper rim and alkylated lower rim, afforded the CA₄-Man3-NPs in a controllable manner. The presence of thiourea units between calixarene and tri-mannose moiety facilitated the formation of a stable core with bidentate hydrogen bonds, which in turn promoted mannose receptor targeted uptake and helped in the intracellular pH-responsive release of antineoplastic doxorubicin (Dox). Physiochemical features including the stability of the nanomicelle could circumvent the undesirable leakage of the cargoes, ensuring maximum therapeutic output with minimum off-targeted toxicity. Most importantly, surface-enhanced Raman scattering (SERS) was utilized for the first time to evaluate the critical micelle concentration during the formation, cellular uptake and intracellular drug release. The present study not only provides an architectural design of a new class of organic small molecular nanomicelles but also unveils a robust self-assembly approach that paves the way for the delivery of a wide range of hydrophobic chemotherapeutic drugs.

碳水化合物-凝集素相互作用和乙二醇-分子驱动的自组装是为生物医学应用创造超分子纳米结构的强大而具有挑战性的策略。在此，我们开发了一种模块化的胶束化方法，使用小分子甘露糖基化杯[4]芳烃合成核心CA ₄ -Man3生成纳米胶束CA ₄ -Man3-NPs，它可以靶向癌细胞表面受体并促进疏水性货物的交付。杯[4]芳烃的低聚性质使杯[4]芳烃（CA ₄）的动态自组装成为可能，其中两亲物在上缘和烷基化下缘用甘露糖单元（CA-糖共轭物）官能化，提供加利福尼亚州₄ -Man3-NPs以可控的方式。杯芳烃和三甘露糖部分之间硫脲单元的存在促进了具有双齿氢键的稳定核心的形成，这反过来又促进了甘露糖受体的靶向摄取并有助于抗肿瘤多柔比星 (Dox) 的细胞内 pH 响应释放。包括纳米胶束稳定性在内的物理化学特征可以避免货物的不良泄漏，确保最大的治疗输出和最小的脱靶毒性。最重要的是，首次利用表面增强拉曼散射 (SERS) 来评估形成、细胞摄取和细胞内药物释放过程中的临界胶束浓度。