Green-Synthesized Nanomaterials for Targeted Drug Delivery Recent Advances, Mechanisms and Translational Challenges

Abstract

Targeted drug delivery systems have revolutionized modern therapeutics by enabling site-specific drug accumulation while minimizing systemic toxicity and adverse effects. However, the clinical translation of many conventional nanocarriers remains limited due to concerns regarding biocompatibility, environmental impact, and manufacturing complexity. Green-synthesized nanomaterials have emerged as promising alternatives, utilizing plant extracts, microorganisms, and naturally derived biomolecules to produce sustainable and biologically compatible nanocarriers. Their unique surface chemistry and bioactive capping agents enhance stability, cellular interactions, and therapeutic performance. Recent advances have expanded the application of green nanocarriers in cancer therapy, brain-targeted delivery, gene and RNA therapeutics, antimicrobial treatment, and theranostic platforms. Their efficacy is governed by complex nano–bio interactions, including passive and active targeting mechanisms, stimuli-responsive drug release, and intracellular trafficking pathways. Surface functionalization and biomimetic engineering have further improved targeting precision and controlled drug release. Despite encouraging preclinical outcomes, significant translational barriers persist. Variability in green synthesis protocols, challenges in large-scale manufacturing, limited long-term safety data, and the absence of standardized regulatory frameworks continue to impede clinical adoption. This review critically discusses the mechanistic principles, recent advances, and translational challenges of green-synthesized nanomaterials for targeted drug delivery. Future integration of artificial intelligence-driven design, personalized nanomedicine, and sustainable pharmaceutical manufacturing may accelerate the development of clinically viable and environmentally responsible nanotherapeutic systems.