Current situation and challenges of polyhydroxyalkanoates-derived nanocarriers for cancer therapy

The sustained-release system for chemotherapeutic drugs or photosensitizer based on drug-loaded biopolyester nanocarriers can effectively reduce the overall dosage and frequency of administration, thereby mitigating side effects such as immunosuppression and drug resistance caused by prolonged chemotherapy. Compared to polylactic acid (PLA), microorganism-derived polyhydroxyalkanoates (PHAs) exhibits superior biocompatibility and more flexible drug release behavior due to their diverse monomer compositions, slower degradation behavior, and milder acidic degradation products, 3-hydroxybutyric acid (3HB). It explains PHAs are more suitable carriers for chemotherapeutic drugs. In this review, we summarize the current situation of PHA-derived nanocarriers (PHA-NCs) for cancer therapy, including the advantages, preparation methods, and anticancer applications. Furthermore, we also analyzed the current limitations in the application of PHA-NCs for cancer therapy and proposed existing challenges along with strategies for future development. With the rapid advancements in synthetic biology and nanomedicine, we believe that PHA will once again attract significant attention. • Polyhydroxyalkanoates (PHAs) are more suitable nanocarriers for chemotherapeutic drugs and photosensitizers due to their superior biocompatibility and more flexible drug release behavior. • Most PHA nanocarriers (PHA-NCs) lacks systematic animal studies, limiting their clinical use in cancer treatment. • Five challenges of PHA-NCs for cancer therapy: Lower cost, Stability, Solvent safety, Targeting and Safe, convenient delivery.