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Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review
Abstract
As the mainstay in the treatment of various cancers, chemotherapy plays a vital role, but still faces many challenges, such as poor tumour selectivity and multidrug resistance (MDR). Targeted drug delivery using nanotechnology has provided a new strategy for addressing the limitations of the conventional chemotherapy. In the last decade, the volume of research published in this area has increased tremendously, especially with functional nano drug delivery systems (nanocarriers). Coupling a specific stimuli-triggered drug release mechanism with these delivery systems is one of the most prevalent approaches for improving therapeutic outcomes. Among the various stimuli, pH triggered delivery is regarded as the most general strategy, targeting the acidic extracellular microenvironment and intracellular organelles of solid tumours. In this review, we discuss recent advances in the development of pH-sensitive nanocarriers for tumour-targeted drug delivery. The review focuses on the chemical design of pH-sensitive biomaterials, which are used to fabricate nanocarriers for extracellular and/or intracellular tumour site-specific drug release. The pH-responsive biomaterials bring forth conformational changes in these nanocarriers through various mechanisms such as protonation, charge reversal or cleavage of a chemical bond, facilitating tumour specific cell uptake or drug release. A greater understanding of these mechanisms will help to design more efficient drug delivery systems to address the challenges encountered in conventional chemotherapy.
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“Acidic pH caused protonation leads to hydrophilic-hydrophobic phase transition for the anionic polymers, and hydrophobic- hydrophilic phase transition for cationic polymers, inducing deformation of amphiphilic structures leading to drug release [136].”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [136]
In the citing paper
“Generally, two basic perceptions define the mechanism of the pH-responsive nanoparticles, such as the cleavage of chemical bonds and nanocarrier protonation.138”
From Smart nanoparticles for cancer therapy (2023) · cites this paper as [138]
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Programmable mRNA Nanotherapeutics through Logic Switch Design
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Stimuli‐Responsive Nanomaterials
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“…ranging from 6.5 to 6.9, whereas normal tissues remain close to physiological pH [167,168]. pH-responsive nanomedicines exploit this gradient through acid-cleavable chemical bonds, protonation-induced charge reversal, polymer swelling, phase transitions, or carrier disintegration [169,170].”
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Metadata
- Authors
- Kanamala, M., Wilson, W. R., Yang, M., Palmer, B. D., & Wu, Z.
- Affiliations
- University of Auckland (NZ)
- Corresponding author
- Wu, Zimei
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 85
- Pages
- 152-167
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2288119981
- Cited by
- 1,004
- References
- 213
- Citations by year
- 2026: 65 · 2025: 96 · 2024: 78 · 2023: 85 · 2022: 99 · 2021: 117 · 2020: 129 · 2019: 113 · 2018: 108 · 2017: 77 · 2016: 37
- FWCI
- 5.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- ResearchSpace (University of Auckland) (submittedVersion)
- Funders
- Royal Society of New Zealand (UOA1201)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- pH-responsive nanocarriers, tumour-targeted drug delivery, stimuli-responsive drug release, intracellular drug release, protonation, charge reversal, bond cleavage, tumor selectivity, multidrug resistance, chemotherapy
- MeSH terms
- Animals, Biocompatible Materials, Clinical Trials as Topic, Disease Models, Animal, Humans, Hydrogen-Ion Concentration, Neoplasms, Drug Delivery Systems, Nanotechnology, Nanostructures, Drug Liberation
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