Dudhat Kiran, Pirojiya Harsh, Bhalala Krupali, Mori Dhaval, Prajapati Bhupendra
School of Pharmacy, RK University, Kasturbadham, Rajkot, India.
B. K. Modi Government Pharmacy College, Gujarat Technological University, Rajkot, India.
AAPS PharmSciTech. 2025 Jul 14;26(6):190. doi: 10.1208/s12249-025-03175-8.
Phospholipid-drug conjugates (PDCs) represent a novel advancement in cancer therapy, combining the therapeutic potential of active drug molecules with the biocompatibility and targeting benefits of phospholipids. Conventional cancer treatments face limitations such as drug resistance, off-target toxicity, and poor solubility. PDCs address these issues by enhancing drug stability, bioavailability, and targeted delivery, reducing systemic toxicity. Their amphiphilic nature enables self-assembly into nanocarriers, allowing controlled and site-specific drug release. PDCs utilize both passive and active targeting mechanisms, with the enhanced permeability and retention (EPR) effect facilitating tumor accumulation and ligand-receptor interactions enhancing active targeting. Stimuli-responsive PDCs further improve specificity by releasing drugs in response to tumor microenvironment factors such as acidity and enzymatic activity. Recent advances in PDC synthesis, including covalent bonding strategies, modular designs, and bio-inspired approaches, have broadened their therapeutic potential. Their integration with nanotechnology and gene-based therapies presents new possibilities for precision medicine and personalized treatment. Despite these benefits, challenges such as scalability, regulatory hurdles, and multidrug resistance (MDR) remain. Research is addressing these issues through AI-driven optimization, bioprinting-based formulations, and sustainable green chemistry. Future applications extend beyond oncology, with potential uses in neurodegenerative, infectious, and cardiovascular diseases. Overall, PDCs hold tremendous promise in transforming cancer treatment, offering safer, more effective, and highly targeted therapies that could revolutionize patient outcomes and therapeutic precision.
磷脂 - 药物偶联物（PDCs）代表了癌症治疗领域的一项新进展，它将活性药物分子的治疗潜力与磷脂的生物相容性和靶向优势相结合。传统的癌症治疗方法面临着诸如耐药性、脱靶毒性和溶解性差等局限性。PDCs通过提高药物稳定性、生物利用度和靶向递送能力来解决这些问题，从而降低全身毒性。它们的两亲性使其能够自组装成纳米载体，实现可控的和位点特异性的药物释放。PDCs利用被动和主动靶向机制，增强的渗透和滞留（EPR）效应促进肿瘤蓄积，而配体 - 受体相互作用则增强主动靶向。刺激响应性PDCs通过响应肿瘤微环境因素（如酸度和酶活性）释放药物，进一步提高了特异性。PDCs合成方面的最新进展，包括共价键合策略、模块化设计和仿生方法，拓宽了它们的治疗潜力。它们与纳米技术和基于基因的疗法的结合为精准医学和个性化治疗带来了新的可能性。尽管有这些优势，但仍存在诸如可扩展性、监管障碍和多药耐药性（MDR）等挑战。研究正在通过人工智能驱动的优化、基于生物打印的制剂和可持续绿色化学来解决这些问题。未来的应用将超越肿瘤学领域，在神经退行性疾病、传染病和心血管疾病方面具有潜在用途。总体而言，PDCs在变革癌症治疗方面具有巨大潜力，提供更安全、更有效且高度靶向的疗法，可能会彻底改变患者的治疗效果和治疗精准度。
