Santhamoorthy Madhappan, Asaithambi Perumal, Ramkumar Vanaraj, Elangovan Natarajan, Perumal Ilaiyaraja, Kim Seong Cheol
School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea.
Department of Water Supply and Environmental Engineering, Faculty of Civil and Environmental Engineering, Jimma Institute of Technology, Jimma University, Jimma P.O. Box 378, Ethiopia.
Polymers (Basel). 2025 Jun 13;17(12):1640. doi: 10.3390/polym17121640.
Mesoporous silica nanoparticles (MSNs) are gaining popularity in nanomedicine due to their large surface area, variable pore size, great biocompatibility, and chemical adaptability. In recent years, the combination of smart polymeric materials with MSNs has transformed the area of regulated drug administration, particularly under stimuli-responsive settings. Polymer-modified MSNs provide increased stability, longer circulation times, and, most crucially, the capacity to respond to diverse internal (pH, redox potential, enzymes, and temperature) and external (light, magnetic field, and ultrasonic) stimuli. These systems allow for the site-specific, on-demand release of therapeutic molecules, increasing treatment effectiveness while decreasing off-target effects. This review presents a comprehensive analysis of recent advancements in the development and application of polymer-functionalized MSNs for stimuli-triggered drug delivery. Key polymeric modifications, including thermoresponsive, pH-sensitive, redox-responsive, and enzyme-degradable systems, are discussed in terms of their design strategies and therapeutic outcomes. The synergistic use of dual or multiple stimuli-responsive polymers is also highlighted as a promising avenue to enhance precision and control in complex biological environments. Moreover, the integration of targeting ligands and stealth polymers such as PEG further enables selective tumor targeting and immune evasion, broadening the potential clinical applications of these nanocarriers. Recent progress in stimuli-triggered MSNs for combination therapies such as chemo-photothermal and chemo-photodynamic therapy is also covered, emphasizing how polymer modifications enhance responsiveness and therapeutic synergy. Finally, the review discusses current challenges, including scalability, biosafety, and regulatory considerations, and provides perspectives on future directions to bridge the gap between laboratory research and clinical translation.
介孔二氧化硅纳米颗粒（MSNs）因其大表面积、可变孔径、良好的生物相容性和化学适应性而在纳米医学领域越来越受欢迎。近年来，智能高分子材料与MSNs的结合改变了药物控释领域，特别是在刺激响应环境下。聚合物修饰的MSNs具有更高的稳定性、更长的循环时间，最关键的是能够响应多种内部（pH值、氧化还原电位、酶和温度）和外部（光、磁场和超声波）刺激。这些系统允许治疗分子进行位点特异性的按需释放，提高治疗效果，同时减少脱靶效应。本文综述了聚合物功能化MSNs在刺激触发药物递送方面的最新进展。重点讨论了关键的聚合物修饰，包括热响应、pH敏感、氧化还原响应和酶可降解系统的设计策略和治疗效果。双刺激或多刺激响应聚合物的协同使用也被强调为在复杂生物环境中提高精度和控制的一条有前景的途径。此外，靶向配体和隐形聚合物（如PEG）的整合进一步实现了选择性肿瘤靶向和免疫逃逸，拓宽了这些纳米载体的潜在临床应用。本文还介绍了刺激触发的MSNs在联合治疗（如化疗-光热和化疗-光动力治疗）方面的最新进展，强调了聚合物修饰如何增强响应性和治疗协同作用。最后，本文讨论了当前面临的挑战，包括可扩展性、生物安全性和监管方面的考虑，并对未来方向提出了展望，以弥合实验室研究与临床转化之间的差距。
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