Journal
JOURNAL OF CONTROLLED RELEASE
Volume 349, Issue -, Pages 963-982Publisher
ELSEVIER
DOI: 10.1016/j.jconrel.2022.08.005
Keywords
Cancer therapy; Drug delivery; pH-responsive; Poly(L-histidine); Polypeptides
Funding
- Shanghai Sailing Program [22YF1417700]
- Korean Government (MSIT) [2021R1A2C2003685]
- National Research Foundation of Korea grant
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Stimuli-responsive drug delivery systems based on polymeric nanovehicles can release drugs according to the acidic tumor microenvironment, improving treatment specificity and efficacy.
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 chemo-therapeutic agents. Herein, we highlight the state-of-the-art design and construction of pH-responsive nano -vehicles based on PLH and discuss the future challenges and perspectives of this fascinating biomaterial for targeted cancer treatment and benchtop-to-clinic translation.
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