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Delivery of Chemotherapy Agents and Nucleic Acids with pH-Dependent Nanoparticles

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PHARMACEUTICS
卷 15, 期 5, 页码 -

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MDPI
DOI: 10.3390/pharmaceutics15051482

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polymers; pH-sensitive; nucleic acids; siRNA; chemotherapy; nanoparticles; carriers; tumor pH

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In order to improve the accuracy of targeted therapy, a new approach has been developed to target and release therapy using the acidic pH of the tumor extracellular matrix and endosomes. By using pH-responsive nanoparticles to accumulate in the tumor and release the treatment in lower pH environments, greater specificity and targeting can be achieved. However, these pH-sensitive strategies are still in early stages of development with potential obstacles that may limit their clinical use.
With less than one percent of systemically injected nanoparticles accumulating in tumors, several novel approaches have been spurred to direct and release the therapy in or near tumors. One such approach depends on the acidic pH of the extracellular matrix and endosomes of the tumor. With an average pH of 6.8, the extracellular tumor matrix provides a gradient for pH-responsive particles to accumulate, enabling greater specificity. Upon uptake by tumor cells, nanoparticles are further exposed to lower pHs, reaching a pH of 5 in late endosomes. Based on these two acidic environments in the tumor, various pH-dependent targeting strategies have been employed to release chemotherapy or the combination of chemotherapy and nucleic acids from macromolecules such as the keratin protein or polymeric nanoparticles. We will review these release strategies, including pH-sensitive linkages between the carrier and hydrophobic chemotherapy agent, the protonation and disruption of polymeric nanoparticles, an amalgam of these first two approaches, and the release of polymers shielding drug-loaded nanoparticles. While several pH-sensitive strategies have demonstrated marked antitumor efficacy in preclinical trials, many studies are early in their development with several obstacles that may limit their clinical use.

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