Khandal Jayesh, Dohare Shubham, Dongsar Tenzin Sonam, Gupta Garima, Alsayari Abdulrhman, Wahab Shadma, Kesharwani Prashant
Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi 110062, India.
Graphic Era Hill University, Dehradun 248002, India; School of Allied Medical Sciences, Lovely Professional University, Phagwara, Punjab, India.
Int J Biol Macromol. 2025 May;310(Pt 1):143244. doi: 10.1016/j.ijbiomac.2025.143244. Epub 2025 Apr 17.
Cancer persists as a formidable global health crisis, with conventional therapies often compromised by systemic toxicity, poor tumor specificity, and therapeutic resistance. Nanotechnology has emerged as a transformative approach, leveraging nanoscale materials to enhance drug bioavailability, enable targeted delivery, and mitigate off-target effects. Among these innovations, gelatin-based nanoparticles (GNPs), derived from collagen and endorsed by the FDA have garnered significant attention as biocompatible, biodegradable nanocarriers uniquely suited for oncology applications. GNPs address critical extracellular barriers such as inefficient tumor penetration, rapid clearance, and nonspecific biodistribution by capitalizing on gelatin's intrinsic advantages: low immunogenicity, tumor microenvironment responsiveness (pH, enzymes, redox gradients), and tunable surface functionalization. This review highlights the versatility of GNPs in overcoming these challenges through advanced strategies like ligand-mediated targeting, combinatorial therapies, and size-transformable systems that enhance tumor accumulation and therapeutic precision. Case studies across lung, breast, skin, liver, colorectal, brain, and head/neck cancers demonstrate GNPs' ability to reduce IC50 values by 2 to 4-fold, achieve >90 % apoptosis in malignant cells, and minimize damage to healthy tissues. Despite the challenges in translating gelatin-based nanocarriers from preclinical studies to clinical applications in cancer therapy, their promising preclinical performance highlights their potential as patient-centric platforms capable of advancing precision oncology. Further their adaptability, multifunctionality, and capacity for stimuli-responsive drug release underscore their potential to improve clinical outcomes, offering a targeted, low-toxicity paradigm for managing diverse malignancies.
癌症仍然是一个严峻的全球健康危机，传统疗法常常受到全身毒性、肿瘤特异性差和治疗耐药性的影响。纳米技术已成为一种变革性方法，利用纳米级材料提高药物生物利用度、实现靶向递送并减轻脱靶效应。在这些创新中，由胶原蛋白衍生并得到美国食品药品监督管理局认可的明胶基纳米颗粒（GNPs）作为生物相容性、可生物降解的纳米载体，特别适用于肿瘤学应用，因此受到了广泛关注。GNPs利用明胶的固有优势，即低免疫原性、肿瘤微环境响应性（pH值、酶、氧化还原梯度）和可调节的表面功能化，解决了诸如肿瘤穿透效率低、快速清除和非特异性生物分布等关键的细胞外障碍。本文综述强调了GNPs通过配体介导的靶向、联合疗法和尺寸可转换系统等先进策略克服这些挑战的多功能性，这些策略可增强肿瘤积累和治疗精度。肺癌、乳腺癌、皮肤癌、肝癌、结直肠癌、脑癌和头颈癌的案例研究表明，GNPs能够将IC50值降低2至4倍，使恶性细胞凋亡率达到90%以上，并将对健康组织的损害降至最低。尽管将基于明胶的纳米载体从临床前研究转化为癌症治疗的临床应用存在挑战，但其有前景的临床前表现突出了它们作为以患者为中心的平台的潜力，能够推动精准肿瘤学发展。此外，它们的适应性、多功能性和刺激响应性药物释放能力强调了它们改善临床结果的潜力，为治疗各种恶性肿瘤提供了一种靶向、低毒性的范例。
