Intelligent poly(l-histidine)-based nanovehicles for controlled drug delivery

Stimuli-responsive drug delivery systems based on polymeric nanovehicles are among the most promising treatment regimens for malignant cancers. Such intelligent systems that release payloads in response to the physiological characteristics of tumor sites have several advantages over conventional drug carriers, offering, in particular, enhanced therapeutic effects and decreased toxicity. The tumor microenvironment (TME) is acidic, suggesting the potential of pH-responsive nanovehicles for enhancing treatment specificity and efficacy. The synthetic polypeptide poly(l-histidine) (PLH) is an appropriate candidate for the preparation of pH-responsive nanovehicles because the pKa of PLH (approximately 6.0) is close to the pH of the acidic TME. In addition, the pendent imidazole rings of PLH yield pH-dependent hydrophobic-to-hydrophilic phase transitions in the acidic TME, triggering the destabilization of nanovehicles and the subsequent release of encapsulated chemotherapeutic agents. Herein, we highlight the state-of-the-art design and construction of pH-responsive nanovehicles based on PLH and discuss the future challenges and perspectives of this fascinating biomaterial for targeted cancer treatment and “benchtop-to-clinic” translation. [Display omitted] •Recent advances in poly(L-histidine) (PLH) based pH-responsive nanomedicines for cancer therapy are reviewed.•The structure, properties, and preparation methods of PLH are introduced.•Different kinds of PLH based drug and gene delivery systems are described in detail.•pH-responsive nature of PLH facilitate the specific accumulation of nanomedicines at tumor sites.