Green Synthesis and Functional Design of Polypyrrole-Based Nanomedicines for Cancer Theranostics: A Critical Review...

Nanomedicine has advanced cancer theranostics via targeted delivery and phototherapy, yet many high-performance systems rely on inorganic or metal-intensive materials synthesized through energy-demanding routes, raising concerns about biocompatibility, environmental accumulation, and sustainability. This review re-evaluates polypyrrole (PPy)-based nanomedicines from a green chemistry perspective, shifting focus from performance-centric optimization to sustainability-guided design. PPy, an organic conductive polymer with near-infrared photothermal activity and structural tunability, offers a promising platform. However, pristine PPy suffers from limited functionality, poor biodegradability, and insufficient reactive oxygen species (ROS) generation. Reported FeCl₃-, CuCl₂-, and Fe²⁺/H₂O₂-mediated routes are compared to examine formulation-specific relationships among synthesis conditions, polymer characteristics, redox behavior, ROS-related function, and process burdens. Because the underlying studies differ in composition, processing, purification, and assay conditions, these comparisons are used to identify evidence-supported trade-offs and data gaps rather than to establish a universal causal hierarchy. Green strategies are critically assessed, including one-step carboxylated copolymerization for backbone degradability and metal-polyphenol networks for catalytic ROS amplification. To organize the heterogeneous evidence, this review introduces a PPy-specific dual-axis evidence map that considers process-related sustainability alongside biofunctional performance. This qualitative tool is intended to identify trade-offs and evidence gaps rather than provide a validated sustainability score.