Bio-based nanophotothermal systems as smart drug delivery platforms for multimodal synergistic cancer therapy-a...

Conventional protocols for cancer treatment are usually accompanied by serious limitations, which can be addressed using innovative, minimally invasive methods, such as photothermal therapy (PTT). But, using this method as a standalone therapy is usually accompanied by uneven heat distribution within tumor tissues, and the risk of cancer recurrence. Integrating PTT with complementary therapeutic modalities can help prevent these issues. The development of nanophotothermal systems (NPTSs) as multipurpose, multimodal platforms for smart drug delivery has greatly broadened the therapeutic landscape of cancer treatment. Additionally, recent developments in bio-based and biocompatible nanomaterials have further expanded the potential of NPTSs in clinical applications. Furthermore, NPTSs combine therapeutic functionalities and diagnostic imaging, i.e., tracking modalities, such as photoacoustic, magnetic resonance, or fluorescence imaging, to provide real-time monitoring of drug delivery and treatment response. Translation of preclinical trials into clinical applications for these systems remains challenging due to issues such as toxicity, biodegradability, scalability, standardization, and regulatory approval. This narrative review analyzes two of the most versatile natural polysaccharides, chitosan (CS) and hyaluronic acid (HA), which have complementary physicochemical and biological properties. Covering the advantages of CS and HA for the application in multifuntional and multimodal nanophotothermal systems, their complementary effects, as well as their functional implications in therapeutic settings, this work aims to create a framework that will serve as a basis for further research in optimizing the design of multifunctional drug-delivery nanosystems, and at the same time, facilitate the transition of photothermal therapy from the bench to clinical use.